9-125307598-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001282680.3(GAPVD1):c.1251+51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 1,582,236 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (590 hom.)
• Consequence: GAPVD1 NM_001282680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

Genes affected

GAPVD1 (HGNC:23375): (GTPase activating protein and VPS9 domains 1) Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-125307598-G-A is Benign according to our data. Variant chr9-125307598-G-A is described in ClinVar as [Benign]. Clinvar id is 1290078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPVD1	NM_001282680.3	c.1251+51G>A		intron_variant		ENST00000297933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPVD1	ENST00000297933.11	c.1251+51G>A		intron_variant		1	NM_001282680.3	P3

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3004 AN: 152142 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.0281 AC: 6884 AN: 244904 Hom.: 351 AF XY: 0.0242 AC XY: 3213 AN XY: 132550

Gnomad AFR exome AF: 0.0276

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.00105

Gnomad EAS exome AF: 0.0842

Gnomad SAS exome AF: 0.0253

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.000359

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.00884 AC: 12643 AN: 1429976 Hom.: 590 Cov.: 25 AF XY: 0.00886 AC XY: 6304 AN XY: 711538

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.000547

Gnomad4 EAS exome AF: 0.0955

Gnomad4 SAS exome AF: 0.0244

Gnomad4 FIN exome AF: 0.0000565

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.00998

GnomAD4 genome AF: 0.0199 AC: 3024 AN: 152260 Hom.: 114 Cov.: 32 AF XY: 0.0215 AC XY: 1604 AN XY: 74460

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00388 Hom.: 3

Bravo AF: 0.0264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.010
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs10986696; hg19: chr9-128069877; COSMIC: COSV52927830; COSMIC: COSV52927830;