18-23857967-G-C

Variant names:

Variant summary

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

The NM_198129.4(LAMA3):c.4260G>C(p.Gly1420Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,780 control chromosomes in the GnomAD database, including 268,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19255 hom., cov: 32)

Exomes 𝑓: 0.57 ( 249510 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.294

Variant links:

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

LAMA3 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=-0.78).

BP6

Variant 18-23857967-G-C is Benign according to our data. Variant chr18-23857967-G-C is described in ClinVar as [Benign]. Clinvar id is 403026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-23857967-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA3	NM_198129.4 link	c.4260G>C	p.Gly1420Gly	synonymous_variant	Exon 33 of 75	ENST00000313654.14	NP_937762.2	Q16787-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA3	ENST00000313654.14 link	c.4260G>C	p.Gly1420Gly	synonymous_variant	Exon 33 of 75	1	NM_198129.4	ENSP00000324532.8	Q16787-2
LAMA3	ENST00000399516.7 link	c.4260G>C	p.Gly1420Gly	synonymous_variant	Exon 33 of 74	1		ENSP00000382432.2	Q16787-3A0A0A0MSA0
LAMA3	ENST00000649721.1 link	c.1152G>C	p.Gly384Gly	synonymous_variant	Exon 8 of 48			ENSP00000497885.1	A0A3B3ITG1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72109

AN:

151944

Hom.:

19256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.494

AC:

123290

AN:

249472

Hom.:

33728

AF XY:

0.504

AC XY:

68245

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.616

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.572

AC:

836700

AN:

1461716

Hom.:

249510

Cov.:

AF XY:

0.570

AC XY:

414610

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.474

AC:

72119

AN:

152064

Hom.:

19255

Cov.:

AF XY:

0.466

AC XY:

34615

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.664

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.548

Gnomad4 NFE

AF:

0.616

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.591

Hom.:

8846

Bravo

AF:

0.459

Asia WGS

AF:

0.278

AC:

967

AN:

3478

EpiCase

AF:

0.629

EpiControl

AF:

0.628

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laryngo-onycho-cutaneous syndrome

Benign:1

Jul 10, 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 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.9

DANN

Benign

0.63

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