20-62309417-C-T

Variant summary

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

The NM_005560.6(LAMA5):c.11007G>A(p.Ala3669=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,584,286 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 134 hom., cov: 29)

Exomes 𝑓: 0.0028 ( 149 hom. )

Consequence

LAMA5
NM_005560.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.228

Variant links:

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. 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. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

LAMA5 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=-0.68).

BP6

Variant 20-62309417-C-T is Benign according to our data. Variant chr20-62309417-C-T is described in ClinVar as [Benign]. Clinvar id is 777608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6 linkuse as main transcript	c.11007G>A	p.Ala3669=	synonymous_variant	80/80	ENST00000252999.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7 linkuse as main transcript	c.11007G>A	p.Ala3669=	synonymous_variant	80/80	1	NM_005560.6	P1	O15230-1
LAMA5	ENST00000370691.6 linkuse as main transcript	n.2802G>A		non_coding_transcript_exon_variant	17/17	1
LAMA5	ENST00000495695.1 linkuse as main transcript	n.508G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3606

AN:

151890

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00687

AC:

1393

AN:

202658

Hom.:

AF XY:

0.00520

AC XY:

582

AN XY:

111874

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.00580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00242

Gnomad SAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00276

AC:

3948

AN:

1432278

Hom.:

149

Cov.:

AF XY:

0.00240

AC XY:

1706

AN XY:

711416

show subpopulations

Gnomad4 AFR exome

AF:

0.0885

Gnomad4 AMR exome

AF:

0.00579

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000893

Gnomad4 SAS exome

AF:

0.000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.00602

GnomAD4 genome

AF:

0.0238

AC:

3612

AN:

152008

Hom.:

134

Cov.:

AF XY:

0.0229

AC XY:

1701

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0819

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.00491

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

LAMA5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

6.4

Dann

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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