6-112158839-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001105206.3(LAMA4):c.1710T>C(p.Ser570Ser) 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

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy 1JJ
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LAMA4 links:

ENSG00000237234 (HGNC:):

ENSG00000237234 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
LAMA4	NM_001105206.3 link	c.1710T>C	p.Ser570Ser	synonymous_variant	Exon 14 of 39	ENST00000230538.12	NP_001098676.2	Q16363A0A0A0MQS9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA4	ENST00000230538.12 link	c.1710T>C	p.Ser570Ser	synonymous_variant	Exon 14 of 39	1	NM_001105206.3	ENSP00000230538.7		A0A0A0MQS9

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

GnomAD2 exomes

AF:

0.107

AC:

26756

AN:

251066

AF XY:

0.106

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 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

African (AFR)

AF:

0.0395

AC:

1321

AN:

33450

American (AMR)

AF:

0.130

AC:

5801

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0699

AC:

1826

AN:

26114

East Asian (EAS)

AF:

0.158

AC:

6251

AN:

39660

South Asian (SAS)

AF:

0.110

AC:

9445

AN:

86214

European-Finnish (FIN)

AF:

0.181

AC:

9668

AN:

53360

Middle Eastern (MID)

AF:

0.0692

AC:

399

AN:

5762

European-Non Finnish (NFE)

AF:

0.0891

AC:

98934

AN:

1110092

Other (OTH)

AF:

0.0868

AC:

5235

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

5890

11780

17670

23560

29450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3502

7004

10506

14008

17510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0880

AC:

13395

AN:

152212

Hom.:

782

Cov.:

AF XY:

0.0930

AC XY:

6920

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0414

AC:

1719

AN:

41540

American (AMR)

AF:

0.0905

AC:

1383

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3468

East Asian (EAS)

AF:

0.122

AC:

633

AN:

5190

South Asian (SAS)

AF:

0.108

AC:

519

AN:

4820

European-Finnish (FIN)

AF:

0.185

AC:

1956

AN:

10590

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0986

AC:

6708

AN:

68004

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

617

1234

1850

2467

3084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0876

Hom.:

1354

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

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Dilated cardiomyopathy 1JJ

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.69

CADD

Benign

7.1

(source)

DANN

Benign

0.82

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over