18-6980524-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005559.4(LAMA1):c.6004A>G(p.Lys2002Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,564,944 control chromosomes in the GnomAD database, including 401,658 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 36221 hom., cov: 33)

Exomes 𝑓: 0.72 ( 365437 hom. )

Consequence

LAMA1
NM_005559.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.886197E-7).

BP6

Variant 18-6980524-T-C is Benign according to our data. Variant chr18-6980524-T-C is described in ClinVar as [Benign]. Clinvar id is 1168731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-6980524-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4 link	c.6004A>G	p.Lys2002Glu	missense_variant	Exon 42 of 63	ENST00000389658.4	NP_005550.2	P25391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4 link	c.6004A>G	p.Lys2002Glu	missense_variant	Exon 42 of 63	1	NM_005559.4	ENSP00000374309.3		P25391
LAMA1	ENST00000579014.5 link	n.7019A>G		non_coding_transcript_exon_variant	Exon 41 of 62	2

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104126

AN:

151996

Hom.:

36196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.710

GnomAD3 exomes

AF:

0.735

AC:

184537

AN:

251108

Hom.:

68368

AF XY:

0.733

AC XY:

99532

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.833

Gnomad ASJ exome

AF:

0.730

Gnomad EAS exome

AF:

0.827

Gnomad SAS exome

AF:

0.729

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.715

Gnomad OTH exome

AF:

0.735

GnomAD4 exome

AF:

0.718

AC:

1013922

AN:

1412830

Hom.:

365437

Cov.:

AF XY:

0.718

AC XY:

507326

AN XY:

706436

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.827

Gnomad4 ASJ exome

AF:

0.726

Gnomad4 EAS exome

AF:

0.824

Gnomad4 SAS exome

AF:

0.726

Gnomad4 FIN exome

AF:

0.745

Gnomad4 NFE exome

AF:

0.712

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.685

AC:

104198

AN:

152114

Hom.:

36221

Cov.:

AF XY:

0.690

AC XY:

51300

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.750

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.834

Gnomad4 SAS

AF:

0.732

Gnomad4 FIN

AF:

0.745

Gnomad4 NFE

AF:

0.719

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.714

Hom.:

101664

Bravo

AF:

0.682

TwinsUK

AF:

0.728

AC:

2700

ALSPAC

AF:

0.697

AC:

2688

ESP6500AA

AF:

0.553

AC:

2436

ESP6500EA

AF:

0.715

AC:

6146

ExAC

AF:

0.727

AC:

88298

Asia WGS

AF:

0.788

AC:

2738

AN:

3476

EpiCase

AF:

0.712

EpiControl

AF:

0.719

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Jun 08, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.14

MetaRNN

Benign

6.9e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.7

PrimateAI

Benign

0.21

PROVEAN

Benign

0.97

REVEL

Benign

0.034

Sift

Benign

0.43

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.0080

MPC

0.15

ClinPred

0.0046

GERP RS

3.3

Varity_R

0.039

gMVP

0.082

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