rs1130667

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000228.3(LAMB3):c.384C>T(p.Pro128Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,611,392 control chromosomes in the GnomAD database, including 118,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P128P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.31 ( 8286 hom., cov: 30)

Exomes 𝑓: 0.38 ( 110442 hom. )

Consequence

LAMB3
NM_000228.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.01

Publications

16 publications found

Variant links:

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

LAMB3 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
junctional epidermolysis bullosa Herlitz type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Laboratory for Molecular Medicine
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Ambry Genetics
amelogenesis imperfecta type 1A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
amelogenesis imperfecta type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
generalized junctional epidermolysis bullosa non-Herlitz type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LAMB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 1-209634627-G-A is Benign according to our data. Variant chr1-209634627-G-A is described in ClinVar as Benign. ClinVar VariationId is 255596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB3	NM_000228.3 link	c.384C>T	p.Pro128Pro	synonymous_variant	Exon 6 of 23	ENST00000356082.9	NP_000219.2	Q13751A0A0S2Z3R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMB3	ENST00000356082.9 link	c.384C>T	p.Pro128Pro	synonymous_variant	Exon 6 of 23	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 link	c.384C>T	p.Pro128Pro	synonymous_variant	Exon 6 of 23	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 link	c.384C>T	p.Pro128Pro	synonymous_variant	Exon 5 of 22	1		ENSP00000375778.1	Q13751
LAMB3	ENST00000415782.1 link	c.384C>T	p.Pro128Pro	synonymous_variant	Exon 6 of 6	2		ENSP00000388960.1	Q5THA1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47036

AN:

151696

Hom.:

8286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.322

GnomAD2 exomes

AF:

0.342

AC:

84343

AN:

246344

AF XY:

0.352

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.387

Gnomad EAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.383

AC:

559312

AN:

1459574

Hom.:

110442

Cov.:

AF XY:

0.383

AC XY:

278120

AN XY:

726098

show subpopulations

African (AFR)

AF:

0.132

AC:

4407

AN:

33456

American (AMR)

AF:

0.217

AC:

9691

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

10290

AN:

26106

East Asian (EAS)

AF:

0.250

AC:

9893

AN:

39618

South Asian (SAS)

AF:

0.337

AC:

28987

AN:

86104

European-Finnish (FIN)

AF:

0.461

AC:

24535

AN:

53276

Middle Eastern (MID)

AF:

0.463

AC:

2662

AN:

5744

European-Non Finnish (NFE)

AF:

0.402

AC:

446509

AN:

1110364

Other (OTH)

AF:

0.370

AC:

22338

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

17469

34938

52408

69877

87346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13662

27324

40986

54648

68310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

47034

AN:

151818

Hom.:

8286

Cov.:

AF XY:

0.312

AC XY:

23136

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.139

AC:

5771

AN:

41456

American (AMR)

AF:

0.266

AC:

4059

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1379

AN:

3466

East Asian (EAS)

AF:

0.241

AC:

1227

AN:

5090

South Asian (SAS)

AF:

0.325

AC:

1565

AN:

4820

European-Finnish (FIN)

AF:

0.458

AC:

4836

AN:

10550

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26943

AN:

67850

Other (OTH)

AF:

0.324

AC:

680

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1584

3168

4753

6337

7921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.337

Hom.:

6126

Bravo

AF:

0.288

Asia WGS

AF:

0.315

AC:

1094

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amelogenesis imperfecta type 1A

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Junctional epidermolysis bullosa

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.15

(source)

DANN

Benign

0.66

PhyloP100

-4.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over