6-112158839-A-G

Position:

chr6-112158839-A-G

Variant summary

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

The NM_001105206.3(LAMA4):c.1710T>C(p.Ser570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 1,611,908 control chromosomes in the GnomAD database, including 8,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 782 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7471 hom. )

Consequence

LAMA4
NM_001105206.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.376

Variant links:

Genes affected

LAMA4 (HGNC:6484): (laminin subunit alpha 4) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the alpha chain isoform laminin, alpha 4. The domain structure of alpha 4 is similar to that of alpha 3, both of which resemble truncated versions of alpha 1 and alpha 2, in that approximately 1,200 residues at the N-terminus (domains IV, V and VI) have been lost. Laminin, alpha 4 contains the C-terminal G domain which distinguishes all alpha chains from the beta and gamma chains. The RNA analysis from adult and fetal tissues revealed developmental regulation of expression, however, the exact function of laminin, alpha 4 is not known. Tissue-specific utilization of alternative polyA-signal has been described in literature. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

LAMA4 links:

(HGNC:):

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=-0.69).

BP6

Variant 6-112158839-A-G is Benign according to our data. Variant chr6-112158839-A-G is described in ClinVar as [Benign]. Clinvar id is 44351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-112158839-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.376 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA4	NM_001105206.3 linkuse as main transcript	c.1710T>C	p.Ser570=	synonymous_variant	14/39	ENST00000230538.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA4	ENST00000230538.12 linkuse as main transcript	c.1710T>C	p.Ser570=	synonymous_variant	14/39	1	NM_001105206.3	A1
	ENST00000585373.5 linkuse as main transcript	n.414+875A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0880

AC:

13389

AN:

152094

Hom.:

784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0986

Gnomad OTH

AF:

0.0707

GnomAD3 exomes

AF:

0.107

AC:

26756

AN:

251066

Hom.:

1652

AF XY:

0.106

AC XY:

14373

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.0732

Gnomad EAS exome

AF:

0.0975

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.0970

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0951

AC:

138880

AN:

1459696

Hom.:

7471

Cov.:

AF XY:

0.0964

AC XY:

70039

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.0699

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.0891

Gnomad4 OTH exome

AF:

0.0868

GnomAD4 genome

AF:

0.0880

AC:

13395

AN:

152212

Hom.:

782

Cov.:

AF XY:

0.0930

AC XY:

6920

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0414

Gnomad4 AMR

AF:

0.0905

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.0986

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0853

Hom.:

854

Bravo

AF:

0.0767

Asia WGS

AF:

0.123

AC:

427

AN:

3478

EpiCase

AF:

0.0847

EpiControl

AF:

0.0851

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 16, 2011	- -

Dilated cardiomyopathy 1JJ

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

DANN

Benign

0.82

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