NM_017667.4:c.422+36A>G

Variant names:

• chr7-93257500-A-G
• rs722263
• NM_017667.4:c.422+36A>G

Variant summary

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

The NM_017667.4(VPS50):​c.422+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,177,912 control chromosomes in the GnomAD database, including 120,375 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 0.55 (26433 hom., cov: 32)
  • Exomes 𝑓: 0.42 (93942 hom.)
• Consequence: VPS50 NM_017667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

Genes affected

VPS50 (HGNC:25956): (VPS50 subunit of EARP/GARPII complex) Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [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 (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS50	NM_017667.4	c.422+36A>G		intron_variant	Intron 6 of 27	ENST00000305866.10	NP_060137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS50	ENST00000305866.10	c.422+36A>G		intron_variant	Intron 6 of 27	1	NM_017667.4	ENSP00000307666.5

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82894 AN: 151624 Hom.: 26370 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.465 AC: 99257 AN: 213326 Hom.: 25292 AF XY: 0.445 AC XY: 51718 AN XY: 116142

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.620

Gnomad SAS exome AF: 0.391

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.417 AC: 427787 AN: 1026170 Hom.: 93942 Cov.: 13 AF XY: 0.412 AC XY: 217443 AN XY: 528396

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.547 AC: 83025 AN: 151742 Hom.: 26433 Cov.: 32 AF XY: 0.546 AC XY: 40461 AN XY: 74142

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.508

Alfa AF: 0.415 Hom.: 7555

Bravo AF: 0.573

Asia WGS AF: 0.523 AC: 1812 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs722263; hg19: chr7-92886812; COSMIC: COSV104381521; COSMIC: COSV104381521;