rs4925386

Positions:

• chr20-62345988-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005560.6(LAMA5):​c.1417+93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,582,194 control chromosomes in the GnomAD database, including 354,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (27142 hom., cov: 32)
  • Exomes 𝑓: 0.67 (327617 hom.)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.579

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]

LOC124904946 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-62345988-T-C is Benign according to our data. Variant chr20-62345988-T-C is described in ClinVar as [Benign]. Clinvar id is 1297291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6	c.1417+93A>G		intron_variant		ENST00000252999.7
LOC124904946	XR_007067699.1	n.389T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7	c.1417+93A>G		intron_variant		1	NM_005560.6	P1
LAMA5	ENST00000370677.4	n.1442+93A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85738 AN: 151944 Hom.: 27139 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.672 AC: 961514 AN: 1430132 Hom.: 327617 Cov.: 27 AF XY: 0.672 AC XY: 476871 AN XY: 709932

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.783

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.659

GnomAD4 genome AF: 0.564 AC: 85758 AN: 152062 Hom.: 27142 Cov.: 32 AF XY: 0.567 AC XY: 42137 AN XY: 74320

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.617

Alfa AF: 0.673 Hom.: 60340

Bravo AF: 0.547

Asia WGS AF: 0.660 AC: 2295 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	This variant is associated with the following publications: (PMID: 21761138) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs4925386; hg19: chr20-60921044; COSMIC: COSV53370159; COSMIC: COSV53370159;