ENST00000454189.7:c.4+24841G>A

Variant names:

• chrX-13913666-C-T
• rs11798108
• ENST00000454189.7:c.4+24841G>A

Variant summary

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

The ENST00000454189.7(GPM6B):​c.4+24841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 111,247 control chromosomes in the GnomAD database, including 7,883 homozygotes. There are 13,359 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 (7883 hom., 13359 hem., cov: 23)
• Consequence: GPM6B ENST00000454189.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001318729.2	c.4+24841G>A		intron_variant	Intron 1 of 6		NP_001305658.1
GPM6B	NM_001001994.3	c.4+24841G>A		intron_variant	Intron 1 of 6		NP_001001994.1
GPM6B	XM_011545497.3	c.4+24841G>A		intron_variant	Intron 1 of 7		XP_011543799.1
GPM6B	XM_017029432.2	c.4+24841G>A		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+24841G>A		intron_variant	Intron 1 of 6	1		ENSP00000389915.2
GPM6B	ENST00000398361.7	c.-198+24661G>A		intron_variant	Intron 1 of 6	2		ENSP00000381402.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 45592 AN: 111196 Hom.: 7888 Cov.: 23

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.502

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.410 AC: 45591 AN: 111247 Hom.: 7883 Cov.: 23 AF XY: 0.399 AC XY: 13359 AN XY: 33493

African (AFR) AF: 0.205 AC: 6296 AN: 30760

American (AMR) AF: 0.308 AC: 3237 AN: 10523

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1331 AN: 2635

East Asian (EAS) AF: 0.0609 AC: 217 AN: 3565

South Asian (SAS) AF: 0.260 AC: 688 AN: 2647

European-Finnish (FIN) AF: 0.543 AC: 3177 AN: 5854

Middle Eastern (MID) AF: 0.507 AC: 108 AN: 213

European-Non Finnish (NFE) AF: 0.556 AC: 29377 AN: 52866

Other (OTH) AF: 0.418 AC: 634 AN: 1516

Alfa AF: 0.467 Hom.: 4056

Bravo AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.9
DANN	Benign	0.75
PhyloP100		2.2
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: rs11798108; hg19: chrX-13931785;