rs2179402

Positions:

Variant summary

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

The NM_000228.3(LAMB3):c.1716T>C(p.Cys572Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,613,420 control chromosomes in the GnomAD database, including 441,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42713 hom., cov: 35)

Exomes 𝑓: 0.74 ( 398928 hom. )

Consequence

LAMB3
NM_000228.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.966

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=-0.74).

BP6

Variant 1-209625908-A-G is Benign according to our data. Variant chr1-209625908-A-G is described in ClinVar as [Benign]. Clinvar id is 255587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-209625908-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.966 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB3	NM_000228.3 linkuse as main transcript	c.1716T>C	p.Cys572Cys	synonymous_variant	14/23	ENST00000356082.9	NP_000219.2	Q13751A0A0S2Z3R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMB3	ENST00000356082.9 linkuse as main transcript	c.1716T>C	p.Cys572Cys	synonymous_variant	14/23	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 linkuse as main transcript	c.1716T>C	p.Cys572Cys	synonymous_variant	14/23	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 linkuse as main transcript	c.1716T>C	p.Cys572Cys	synonymous_variant	13/22	1		ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113899

AN:

152116

Hom.:

42675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.771

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.751

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.727

Gnomad OTH

AF:

0.745

GnomAD3 exomes

AF:

0.754

AC:

187810

AN:

249024

Hom.:

70965

AF XY:

0.753

AC XY:

101513

AN XY:

134892

show subpopulations

Gnomad AFR exome

AF:

0.769

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.823

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.732

Gnomad NFE exome

AF:

0.737

Gnomad OTH exome

AF:

0.739

GnomAD4 exome

AF:

0.738

AC:

1078370

AN:

1461186

Hom.:

398928

Cov.:

AF XY:

0.739

AC XY:

536973

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.768

Gnomad4 AMR exome

AF:

0.769

Gnomad4 ASJ exome

AF:

0.824

Gnomad4 EAS exome

AF:

0.838

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.730

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.749

AC:

113992

AN:

152234

Hom.:

42713

Cov.:

AF XY:

0.751

AC XY:

55894

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.771

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.814

Gnomad4 EAS

AF:

0.823

Gnomad4 SAS

AF:

0.740

Gnomad4 FIN

AF:

0.740

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.739

Hom.:

53295

Bravo

AF:

0.751

Asia WGS

AF:

0.736

AC:

2560

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Amelogenesis imperfecta type 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Junctional epidermolysis bullosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.74

CADD

Benign

0.27

DANN

Benign

0.56

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