ENST00000454189.7:c.4+5771A>G

Variant names:

• chrX-13932736-T-C
• rs6654096
• ENST00000454189.7:c.4+5771A>G

Variant summary

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

The ENST00000454189.7(GPM6B):​c.4+5771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 110,851 control chromosomes in the GnomAD database, including 7,216 homozygotes. There are 13,243 hemizygotes in GnomAD. 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 0.41 (7216 hom., 13243 hem., cov: 23)
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 3 publications found

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001318729.2	c.4+5771A>G		intron_variant	Intron 1 of 6		NP_001305658.1
GPM6B	NM_001001994.3	c.4+5771A>G		intron_variant	Intron 1 of 6		NP_001001994.1
GPM6B	XM_011545497.3	c.4+5771A>G		intron_variant	Intron 1 of 7		XP_011543799.1
GPM6B	XM_017029432.2	c.4+5771A>G		intron_variant	Intron 1 of 7		XP_016884921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000454189.7	c.4+5771A>G		intron_variant	Intron 1 of 6	1		ENSP00000389915.2
GPM6B	ENST00000398361.7	c.-198+5591A>G		intron_variant	Intron 1 of 6	2		ENSP00000381402.3

Frequencies

GnomAD3 genomes AF: 0.413 AC: 45808 AN: 110797 Hom.: 7218 Cov.: 23

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.412

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.413 AC: 45821 AN: 110851 Hom.: 7216 Cov.: 23 AF XY: 0.400 AC XY: 13243 AN XY: 33105

African (AFR) AF: 0.378 AC: 11529 AN: 30532

American (AMR) AF: 0.283 AC: 2952 AN: 10435

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1247 AN: 2635

East Asian (EAS) AF: 0.0692 AC: 245 AN: 3539

South Asian (SAS) AF: 0.279 AC: 731 AN: 2621

European-Finnish (FIN) AF: 0.510 AC: 2975 AN: 5828

Middle Eastern (MID) AF: 0.419 AC: 91 AN: 217

European-Non Finnish (NFE) AF: 0.474 AC: 25042 AN: 52860

Other (OTH) AF: 0.397 AC: 600 AN: 1510

Alfa AF: 0.443 Hom.: 20585

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		-0.019
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6654096; hg19: chrX-13950855;