NM_000228.3:c.298+50T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000228.3(LAMB3):c.298+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,231,534 control chromosomes in the GnomAD database, including 61,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7612 hom., cov: 33)

Exomes 𝑓: 0.29 ( 53547 hom. )

Consequence

LAMB3
NM_000228.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.829

Publications

8 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: Orphanet, Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics
amelogenesis imperfecta type 1A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-209638484-A-T is Benign according to our data. Variant chr1-209638484-A-T is described in ClinVar as Benign. ClinVar VariationId is 255593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000228.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAMB3	NM_000228.3	MANE Select	c.298+50T>A	intron	N/A	NP_000219.2	A0A0S2Z3R6
LAMB3	NM_001017402.2		c.298+50T>A	intron	N/A	NP_001017402.1	Q13751
LAMB3	NM_001127641.1		c.298+50T>A	intron	N/A	NP_001121113.1	A0A0S2Z3R6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAMB3	ENST00000356082.9	TSL:1 MANE Select	c.298+50T>A	intron	N/A	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7	TSL:1	c.298+50T>A	intron	N/A	ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5	TSL:1	c.298+50T>A	intron	N/A	ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45228

AN:

150420

Hom.:

7599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.307

GnomAD2 exomes

AF:

0.346

AC:

86095

AN:

249054

AF XY:

0.344

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.294

AC:

317628

AN:

1080994

Hom.:

53547

Cov.:

AF XY:

0.298

AC XY:

165111

AN XY:

554946

show subpopulations

African (AFR)

AF:

0.317

AC:

8377

AN:

26400

American (AMR)

AF:

0.496

AC:

21885

AN:

44100

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

5517

AN:

23802

East Asian (EAS)

AF:

0.710

AC:

27081

AN:

38154

South Asian (SAS)

AF:

0.472

AC:

37324

AN:

79062

European-Finnish (FIN)

AF:

0.244

AC:

12975

AN:

53200

Middle Eastern (MID)

AF:

0.274

AC:

1362

AN:

4966

European-Non Finnish (NFE)

AF:

0.247

AC:

188292

AN:

763162

Other (OTH)

AF:

0.308

AC:

14815

AN:

48148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

11936

23873

35809

47746

59682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5842

11684

17526

23368

29210

<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:

0.301

AC:

45278

AN:

150540

Hom.:

7612

Cov.:

AF XY:

0.310

AC XY:

22807

AN XY:

73602

show subpopulations

African (AFR)

AF:

0.322

AC:

12869

AN:

39984

American (AMR)

AF:

0.405

AC:

6183

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

792

AN:

3470

East Asian (EAS)

AF:

0.722

AC:

3729

AN:

5166

South Asian (SAS)

AF:

0.489

AC:

2359

AN:

4826

European-Finnish (FIN)

AF:

0.237

AC:

2511

AN:

10580

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15958

AN:

67950

Other (OTH)

AF:

0.311

AC:

650

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1573

3146

4720

6293

7866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.256

Hom.:

1051

Bravo

AF:

0.313

Asia WGS

AF:

0.575

AC:

1998

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Amelogenesis imperfecta type 1A (1)

Junctional epidermolysis bullosa gravis of Herlitz (1)

Junctional epidermolysis bullosa, non-Herlitz type (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.8

(source)

DANN

Benign

0.70

PhyloP100

0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over