4-175951769-G-A

Variant names:

• chr4-175951769-G-A
• rs4690647
• ENST00000280187.11:c.-23+50540C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000280187.11(GPM6A):​c.-23+50540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,078 control chromosomes in the GnomAD database, including 22,934 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 (22934 hom., cov: 33)
• Consequence: GPM6A ENST00000280187.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 5 publications found

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]

LOC107984113 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000280187.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6A	NM_005277.5		c.-23+50540C>T		intron	N/A	NP_005268.1
	GPM6A	NM_201592.3		c.4+50540C>T		intron	N/A	NP_963886.1
	GPM6A	NM_001261447.2		c.-7+50540C>T		intron	N/A	NP_001248376.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6A	ENST00000280187.11	TSL:1	c.-23+50540C>T		intron	N/A	ENSP00000280187.7
	GPM6A	ENST00000506894.5	TSL:1	c.4+50540C>T		intron	N/A	ENSP00000421578.1
	GPM6A	ENST00000503397.5	TSL:5	c.13+19104C>T		intron	N/A	ENSP00000422959.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78470 AN: 151960 Hom.: 22931 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.516 AC: 78484 AN: 152078 Hom.: 22934 Cov.: 33 AF XY: 0.518 AC XY: 38535 AN XY: 74332

African (AFR) AF: 0.239 AC: 9931 AN: 41466

American (AMR) AF: 0.635 AC: 9702 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3045 AN: 5180

South Asian (SAS) AF: 0.342 AC: 1649 AN: 4816

European-Finnish (FIN) AF: 0.680 AC: 7180 AN: 10560

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42761 AN: 67990

Other (OTH) AF: 0.542 AC: 1140 AN: 2104

Alfa AF: 0.593 Hom.: 108338

Bravo AF: 0.507

Asia WGS AF: 0.445 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.45
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4690647; hg19: chr4-176872920;