rs7687921

Variant names:

• chr4-175937875-A-T
• rs7687921
• ENST00000280187.11:c.-23+64434T>A

Variant summary

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

The NM_005277.5(GPM6A):​c.-23+64434T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,892 control chromosomes in the GnomAD database, including 3,153 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 0.15 (3153 hom., cov: 32)
• Consequence: GPM6A NM_005277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 6 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005277.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6A	NM_005277.5		c.-23+64434T>A		intron	N/A	NP_005268.1	P51674-1
	GPM6A	NM_201592.3		c.4+64434T>A		intron	N/A	NP_963886.1	P51674-3
	GPM6A	NM_001261447.2		c.-7+64434T>A		intron	N/A	NP_001248376.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPM6A	ENST00000280187.11	TSL:1	c.-23+64434T>A		intron	N/A	ENSP00000280187.7	P51674-1
	GPM6A	ENST00000506894.5	TSL:1	c.4+64434T>A		intron	N/A	ENSP00000421578.1	P51674-3
	GPM6A	ENST00000909881.1		c.-23+65113T>A		intron	N/A	ENSP00000579940.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22939 AN: 151776 Hom.: 3147 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.151 AC: 22974 AN: 151892 Hom.: 3153 Cov.: 32 AF XY: 0.150 AC XY: 11172 AN XY: 74264

African (AFR) AF: 0.366 AC: 15111 AN: 41292

American (AMR) AF: 0.0908 AC: 1386 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3470

East Asian (EAS) AF: 0.125 AC: 649 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4808

European-Finnish (FIN) AF: 0.0504 AC: 534 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0508 AC: 3453 AN: 67966

Other (OTH) AF: 0.141 AC: 298 AN: 2112

Alfa AF: 0.0739 Hom.: 443

Bravo AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		0.20
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: rs7687921; hg19: chr4-176859026;