1-209638541-T-G

Position:

chr1-209638541-T-G

Variant summary

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

The NM_000228.3(LAMB3):c.291A>C(p.Ser97Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,601,282 control chromosomes in the GnomAD database, including 308,745 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. S97S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.56 ( 25024 hom., cov: 32)

Exomes 𝑓: 0.62 ( 283721 hom. )

Consequence

LAMB3
NM_000228.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.889

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-209638541-T-G is Benign according to our data. Variant chr1-209638541-T-G is described in ClinVar as [Benign]. Clinvar id is 255592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-209638541-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.889 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 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.291A>C	p.Ser97Ser	synonymous_variant	4/23	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.291A>C	p.Ser97Ser	synonymous_variant	4/23	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 linkuse as main transcript	c.291A>C	p.Ser97Ser	synonymous_variant	4/23	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 linkuse as main transcript	c.291A>C	p.Ser97Ser	synonymous_variant	3/22	1		ENSP00000375778.1	Q13751
LAMB3	ENST00000415782.1 linkuse as main transcript	c.291A>C	p.Ser97Ser	synonymous_variant	4/6	2		ENSP00000388960.1	Q5THA1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85028

AN:

151932

Hom.:

25022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.675

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.574

GnomAD3 exomes

AF:

0.568

AC:

142705

AN:

251300

Hom.:

42743

AF XY:

0.574

AC XY:

77997

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.444

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.286

Gnomad SAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.599

GnomAD4 exome

AF:

0.619

AC:

896976

AN:

1449232

Hom.:

283721

Cov.:

AF XY:

0.617

AC XY:

445418

AN XY:

721706

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.681

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.706

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.559

AC:

85069

AN:

152050

Hom.:

25024

Cov.:

AF XY:

0.559

AC XY:

41557

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.675

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.718

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.572

Alfa

AF:

0.623

Hom.:

36206

Bravo

AF:

0.536

Asia WGS

AF:

0.390

AC:

1355

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.650

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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 12, 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

-0.81

CADD

Benign

4.3

DANN

Benign

0.50

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