9-125305017-T-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.1030-46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00846 in 1,208,882 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (153 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (110 hom.)
• Consequence: GAPVD1 NM_001282680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302

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=-0.8).
• BP6: Variant 9-125305017-T-C is Benign according to our data. Variant chr9-125305017-T-C is described in ClinVar as [Benign]. Clinvar id is 1264778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPVD1	NM_001282680.3	c.1030-46T>C		intron_variant		ENST00000297933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPVD1	ENST00000297933.11	c.1030-46T>C		intron_variant		1	NM_001282680.3	P3

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4038 AN: 152174 Hom.: 153 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00475

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00938 AC: 2312 AN: 246420 Hom.: 66 AF XY: 0.00800 AC XY: 1066 AN XY: 133242

Gnomad AFR exome AF: 0.0879

Gnomad AMR exome AF: 0.00893

Gnomad ASJ exome AF: 0.00490

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00419

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.00317

Gnomad OTH exome AF: 0.00970

GnomAD4 exome AF: 0.00585 AC: 6184 AN: 1056590 Hom.: 110 Cov.: 14 AF XY: 0.00547 AC XY: 2979 AN XY: 544264

Gnomad4 AFR exome AF: 0.0852

Gnomad4 AMR exome AF: 0.00961

Gnomad4 ASJ exome AF: 0.00542

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00430

Gnomad4 FIN exome AF: 0.000677

Gnomad4 NFE exome AF: 0.00331

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0265 AC: 4041 AN: 152292 Hom.: 153 Cov.: 33 AF XY: 0.0255 AC XY: 1899 AN XY: 74486

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00345

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0144 Hom.: 18

Bravo AF: 0.0305

Asia WGS AF: 0.00895 AC: 31 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.8
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs73668914; hg19: chr9-128067296;