rs73938538

Variant names:

• chr18-7008584-A-C
• rs73938538
• NM_005559.4:c.4026T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-7008584-A-C
• chr18-7008584-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.446
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.4026T>G	p.Val1342Val	synonymous_variant	Exon 28 of 63	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.4026T>G	p.Val1342Val	synonymous_variant	Exon 28 of 63	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.5041T>G		non_coding_transcript_exon_variant	Exon 27 of 62	2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23366 AN: 152028 Hom.: 2420 Cov.: 32

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

GnomAD2 exomes AF: 0.122 AC: 30789 AN: 251384 AF XY: 0.118

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 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.: 33 AF XY: 0.100 AC XY: 72634 AN XY: 726418

African (AFR) AF: 0.303 AC: 10149 AN: 33458

American (AMR) AF: 0.156 AC: 6997 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3274 AN: 26118

East Asian (EAS) AF: 0.0858 AC: 3403 AN: 39674

South Asian (SAS) AF: 0.120 AC: 10319 AN: 86240

European-Finnish (FIN) AF: 0.117 AC: 6255 AN: 53368

Middle Eastern (MID) AF: 0.125 AC: 720 AN: 5764

European-Non Finnish (NFE) AF: 0.0891 AC: 98935 AN: 1110490

Other (OTH) AF: 0.107 AC: 6441 AN: 60328

GnomAD4 genome AF: 0.154 AC: 23407 AN: 152146 Hom.: 2427 Cov.: 32 AF XY: 0.153 AC XY: 11406 AN XY: 74402

African (AFR) AF: 0.292 AC: 12127 AN: 41472

American (AMR) AF: 0.137 AC: 2101 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5172

South Asian (SAS) AF: 0.112 AC: 540 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10604

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0883 AC: 6007 AN: 68008

Other (OTH) AF: 0.136 AC: 286 AN: 2110

Alfa AF: 0.116 Hom.: 748

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25668194) -

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome Benign:1

Aug 19, 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	-0.65
CADD	Benign	0.14
DANN	Benign	0.72
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73938538; hg19: chr18-7008583; COSMIC: COSV67533815;