rs9284954

Positions:

• chr4-175727181-C-A
• chr4-175727181-C-G
• chr4-175727181-C-T

Variant summary

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

The NM_201591.3(GPM6A):​c.38-25414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,902 control chromosomes in the GnomAD database, including 20,296 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 0.52 (20296 hom., cov: 32)
• Consequence: GPM6A NM_201591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

Genes affected

GPM6A (HGNC:4460): (glycoprotein M6A) Predicted to enable calcium channel activity. Involved in neuron migration and stem cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPM6A	NM_201591.3	c.38-25414G>T		intron_variant		ENST00000393658.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPM6A	ENST00000393658.7	c.38-25414G>T		intron_variant		1	NM_201591.3	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78222 AN: 151784 Hom.: 20273 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.515 AC: 78296 AN: 151902 Hom.: 20296 Cov.: 32 AF XY: 0.511 AC XY: 37889 AN XY: 74218

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.528

Alfa AF: 0.533 Hom.: 20029

Bravo AF: 0.522

Asia WGS AF: 0.464 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.50

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: rs9284954; hg19: chr4-176648332;