9-125321310-A-C

Position:

• chr9-125321310-A-C

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.1603-123A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 646,714 control chromosomes in the GnomAD database, including 1,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (282 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1135 hom.)
• Consequence: GAPVD1 NM_001282680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484

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]

GAPVD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-125321310-A-C is Benign according to our data. Variant chr9-125321310-A-C is described in ClinVar as [Benign]. Clinvar id is 1291598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPVD1	NM_001282680.3	c.1603-123A>C		intron_variant		ENST00000297933.11	NP_001269609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPVD1	ENST00000297933.11	c.1603-123A>C		intron_variant		1	NM_001282680.3	ENSP00000297933.6

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7643 AN: 152174 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.0606 AC: 29946 AN: 494422 Hom.: 1135 AF XY: 0.0595 AC XY: 15620 AN XY: 262714

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.0256

Gnomad4 EAS exome AF: 0.0000987

Gnomad4 SAS exome AF: 0.0351

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0535

GnomAD4 genome AF: 0.0502 AC: 7639 AN: 152292 Hom.: 282 Cov.: 32 AF XY: 0.0505 AC XY: 3764 AN XY: 74464

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0704 Hom.: 76

Bravo AF: 0.0433

Asia WGS AF: 0.0150 AC: 53 AN: 3478

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 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs34822905; hg19: chr9-128083589;