1-209615358-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000228.3(LAMB3):c.3432A>G(p.Ser1144Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,612,508 control chromosomes in the GnomAD database, including 118,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15536 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103158 hom. )

Consequence

LAMB3
NM_000228.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.67

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-209615358-T-C is Benign according to our data. Variant chr1-209615358-T-C is described in ClinVar as [Benign]. Clinvar id is 255595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB3	NM_000228.3 link	c.3432A>G	p.Ser1144Ser	synonymous_variant	Exon 23 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.3432A>G	p.Ser1144Ser	synonymous_variant	Exon 23 of 23	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 link	c.3432A>G	p.Ser1144Ser	synonymous_variant	Exon 23 of 23	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 link	c.3432A>G	p.Ser1144Ser	synonymous_variant	Exon 22 of 22	1		ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66644

AN:

151998

Hom.:

15520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.394

AC:

98338

AN:

249352

Hom.:

19974

AF XY:

0.390

AC XY:

52631

AN XY:

134892

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.416

Gnomad SAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.373

AC:

544006

AN:

1460392

Hom.:

103158

Cov.:

AF XY:

0.373

AC XY:

270932

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.618

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.401

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.439

AC:

66704

AN:

152116

Hom.:

15536

Cov.:

AF XY:

0.437

AC XY:

32518

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.611

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.408

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.384

Hom.:

7766

Bravo

AF:

0.443

Asia WGS

AF:

0.406

AC:

1416

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.86

CADD

Benign

0.035

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over