20-62363592-C-T

Position:

• chr20-62363592-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005560.6(LAMA5):​c.298-1040G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,842 control chromosomes in the GnomAD database, including 34,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34312 hom., cov: 31)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA5	NM_005560.6	c.298-1040G>A		intron_variant		ENST00000252999.7	NP_005551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7	c.298-1040G>A		intron_variant		1	NM_005560.6	ENSP00000252999.3
LAMA5	ENST00000370677.4	n.323-1040G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100938 AN: 151724 Hom.: 34291 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.709

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.665 AC: 100987 AN: 151842 Hom.: 34312 Cov.: 31 AF XY: 0.671 AC XY: 49816 AN XY: 74214

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.712

Alfa AF: 0.664 Hom.: 8544

Bravo AF: 0.667

Asia WGS AF: 0.758 AC: 2634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs659822; hg19: chr20-60938648;