Variant 18-6958610-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005559.4(LAMA1):c.7831A>C(p.Thr2611Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,130 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2611A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0075 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 11 hom. )

Consequence

LAMA1
NM_005559.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.164

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004136771).

BP6

Variant 18-6958610-T-G is Benign according to our data. Variant chr18-6958610-T-G is described in ClinVar as [Benign]. Clinvar id is 786327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00747 (1138/152274) while in subpopulation AFR AF= 0.0253 (1049/41514). AF 95% confidence interval is 0.024. There are 19 homozygotes in gnomad4. There are 539 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA1	NM_005559.4 linkuse as main transcript	c.7831A>C	p.Thr2611Pro	missense_variant	55/63	ENST00000389658.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LAMA1	ENST00000389658.4 linkuse as main transcript	c.7831A>C	p.Thr2611Pro	missense_variant	55/63	1	NM_005559.4	P1
LAMA1	ENST00000488064.5 linkuse as main transcript	n.1238A>C		non_coding_transcript_exon_variant	6/14	2
LAMA1	ENST00000488089.1 linkuse as main transcript	n.1408A>C		non_coding_transcript_exon_variant	2/3	2
LAMA1	ENST00000579014.5 linkuse as main transcript	n.8846A>C		non_coding_transcript_exon_variant	54/62	2

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1133

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00191

AC:

479

AN:

251396

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000807

AC:

1179

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

518

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00747

AC:

1138

AN:

152274

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

539

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0000227

Hom.:

758

ExAC

AF:

0.00246

AC:

299

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.86

DANN

Benign

0.58

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.059

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

2.7

N;.

REVEL

Benign

0.16

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.083

MVP

0.40

MPC

0.14

ClinPred

0.0072

GERP RS

-1.2

Varity_R

0.043

gMVP

0.53

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