Variant rs73938538 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005559.4(LAMA1):c.4026T>G(p.Val1342Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,612,296 control chromosomes in the GnomAD database, including 10,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2427 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8304 hom. )

Consequence

LAMA1
NM_005559.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.446

Variant links:

Genes affected

LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

LAMA1 links:

LAMA1 (HGNC:):

LAMA1 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=-0.65).

BP6

Variant 18-7008584-A-C is Benign according to our data. Variant chr18-7008584-A-C is described in ClinVar as [Benign]. Clinvar id is 1300106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.446 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA1	NM_005559.4 linkuse as main transcript	c.4026T>G	p.Val1342Val	synonymous_variant	28/63	ENST00000389658.4	NP_005550.2	P25391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4 linkuse as main transcript	c.4026T>G	p.Val1342Val	synonymous_variant	28/63	1	NM_005559.4	ENSP00000374309.3		P25391
LAMA1	ENST00000579014.5 linkuse as main transcript	n.5041T>G		non_coding_transcript_exon_variant	27/62	2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23366

AN:

152028

Hom.:

2420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0884

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.122

AC:

30789

AN:

251384

Hom.:

2236

AF XY:

0.118

AC XY:

16049

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.0916

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.100

AC:

146493

AN:

1460150

Hom.:

8304

Cov.:

AF XY:

0.100

AC XY:

72634

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0858

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.0891

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.154

AC:

23407

AN:

152146

Hom.:

2427

Cov.:

AF XY:

0.153

AC XY:

11406

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0883

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.115

Hom.:

702

Bravo

AF:

0.164

Asia WGS

AF:

0.112

AC:

389

AN:

3478

EpiCase

AF:

0.0878

EpiControl

AF:

0.0916

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2021	This variant is associated with the following publications: (PMID: 25668194) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

Benign:1

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

-0.65

CADD

Benign

0.14

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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