1-209632550-C-G

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.822+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,590,144 control chromosomes in the GnomAD database, including 15,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1330 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13899 hom. )

Consequence

LAMB3
NM_000228.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.421

Publications

3 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=-0.75).

BP6

Variant 1-209632550-C-G is Benign according to our data. Variant chr1-209632550-C-G is described in ClinVar as Benign. ClinVar VariationId is 255597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 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.822+33G>C	intron	N/A	NP_000219.2	A0A0S2Z3R6
LAMB3	NM_001017402.2		c.822+33G>C	intron	N/A	NP_001017402.1	Q13751
LAMB3	NM_001127641.1		c.822+33G>C	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.822+33G>C	intron	N/A	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7	TSL:1	c.822+33G>C	intron	N/A	ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5	TSL:1	c.822+33G>C	intron	N/A	ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19029

AN:

152170

Hom.:

1331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0755

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.137

GnomAD2 exomes

AF:

0.136

AC:

33487

AN:

246656

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.0802

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.0787

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.135

AC:

193419

AN:

1437856

Hom.:

13899

Cov.:

AF XY:

0.134

AC XY:

95612

AN XY:

716100

show subpopulations

African (AFR)

AF:

0.0752

AC:

2479

AN:

32954

American (AMR)

AF:

0.159

AC:

7062

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

6130

AN:

25904

East Asian (EAS)

AF:

0.0980

AC:

3872

AN:

39494

South Asian (SAS)

AF:

0.0890

AC:

7619

AN:

85572

European-Finnish (FIN)

AF:

0.177

AC:

9442

AN:

53356

Middle Eastern (MID)

AF:

0.0949

AC:

505

AN:

5320

European-Non Finnish (NFE)

AF:

0.136

AC:

148630

AN:

1091412

Other (OTH)

AF:

0.129

AC:

7680

AN:

59402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

7992

15983

23975

31966

39958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5186

10372

15558

20744

25930

<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:

0.125

AC:

19044

AN:

152288

Hom.:

1330

Cov.:

AF XY:

0.126

AC XY:

9412

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0805

AC:

3348

AN:

41576

American (AMR)

AF:

0.147

AC:

2254

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.0753

AC:

390

AN:

5178

South Asian (SAS)

AF:

0.0928

AC:

448

AN:

4828

European-Finnish (FIN)

AF:

0.187

AC:

1977

AN:

10598

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9388

AN:

68008

Other (OTH)

AF:

0.138

AC:

291

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

859

1718

2577

3436

4295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.110

Hom.:

253

Bravo

AF:

0.120

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

-0.75

CADD

Benign

0.79

(source)

DANN

Benign

0.79

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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