chr18-23833905-T-C

Position:

chr18-23833905-T-C

Variant summary

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

The NM_198129.4(LAMA3):c.2901T>C(p.Ala967=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,613,790 control chromosomes in the GnomAD database, including 381,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31991 hom., cov: 32)

Exomes 𝑓: 0.69 ( 349245 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.667

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=-0.9).

BP6

Variant 18-23833905-T-C is Benign according to our data. Variant chr18-23833905-T-C is described in ClinVar as [Benign]. Clinvar id is 403025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-23833905-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.667 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA3	NM_198129.4 linkuse as main transcript	c.2901T>C	p.Ala967=	synonymous_variant	24/75	ENST00000313654.14	NP_937762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA3	ENST00000313654.14 linkuse as main transcript	c.2901T>C	p.Ala967=	synonymous_variant	24/75	1	NM_198129.4	ENSP00000324532	P1	Q16787-2
LAMA3	ENST00000399516.7 linkuse as main transcript	c.2901T>C	p.Ala967=	synonymous_variant	24/74	1		ENSP00000382432		Q16787-3
LAMA3	ENST00000591749.1 linkuse as main transcript	n.142T>C		non_coding_transcript_exon_variant	2/3	4
LAMA3	ENST00000592519.1 linkuse as main transcript			upstream_gene_variant		3		ENSP00000467662

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97859

AN:

151888

Hom.:

31988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.709

GnomAD3 exomes

AF:

0.660

AC:

164624

AN:

249526

Hom.:

55397

AF XY:

0.666

AC XY:

90163

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.689

AC:

1007421

AN:

1461784

Hom.:

349245

Cov.:

AF XY:

0.689

AC XY:

500865

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.529

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.702

Gnomad4 OTH exome

AF:

0.700

GnomAD4 genome

AF:

0.644

AC:

97906

AN:

152006

Hom.:

31991

Cov.:

AF XY:

0.641

AC XY:

47639

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.602

Gnomad4 ASJ

AF:

0.776

Gnomad4 EAS

AF:

0.754

Gnomad4 SAS

AF:

0.626

Gnomad4 FIN

AF:

0.640

Gnomad4 NFE

AF:

0.701

Gnomad4 OTH

AF:

0.703

Alfa

AF:

0.682

Hom.:

19423

Bravo

AF:

0.640

Asia WGS

AF:

0.654

AC:

2276

AN:

3478

EpiCase

AF:

0.717

EpiControl

AF:

0.722

ClinVar

Significance: Benign

Submissions summary: Benign:7

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	Dec 13, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Laryngo-onycho-cutaneous syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

DANN

Benign

0.45

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

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