rs3809828

chr17-7343532-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014716.4(ACAP1):c.498C>T(p.Tyr166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,613,662 control chromosomes in the GnomAD database, including 3,040 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 0.050 (292 hom., cov: 31)
  • Exomes 𝑓: 0.057 (2748 hom.)
• Consequence: ACAP1 NM_014716.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

ACAP1 (HGNC:16467): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 1) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in protein transport and regulation of catalytic activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAP1	NM_014716.4	c.498C>T	p.Tyr166=	synonymous_variant	6/22	ENST00000158762.8
ACAP1	XM_047437150.1	c.276C>T	p.Tyr92=	synonymous_variant	6/22
ACAP1	XM_047437151.1	c.276C>T	p.Tyr92=	synonymous_variant	5/21
ACAP1	XM_047437152.1	c.498C>T	p.Tyr166=	synonymous_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAP1	ENST00000158762.8	c.498C>T	p.Tyr166=	synonymous_variant	6/22	1	NM_014716.4	P1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7664 AN: 152078 Hom.: 292 Cov.: 31

Gnomad AFR AF: 0.00985

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0527

GnomAD3 exomes AF: 0.0644 AC: 16136 AN: 250410 Hom.: 710 AF XY: 0.0635 AC XY: 8603 AN XY: 135444

Gnomad AFR exome AF: 0.00877

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.0316

Gnomad EAS exome AF: 0.154

Gnomad SAS exome AF: 0.0502

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0623

Gnomad OTH exome AF: 0.0619

GnomAD4 exome AF: 0.0571 AC: 83519 AN: 1461466 Hom.: 2748 Cov.: 31 AF XY: 0.0567 AC XY: 41239 AN XY: 727010

Gnomad4 AFR exome AF: 0.00786

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0483

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0562

GnomAD4 genome AF: 0.0504 AC: 7671 AN: 152196 Hom.: 292 Cov.: 31 AF XY: 0.0519 AC XY: 3860 AN XY: 74414

Gnomad4 AFR AF: 0.00982

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0556 Hom.: 344

Bravo AF: 0.0459

Asia WGS AF: 0.109 AC: 378 AN: 3478

EpiCase AF: 0.0591

EpiControl AF: 0.0596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	11
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3809828; hg19: chr17-7246851; COSMIC: COSV50134455; COSMIC: COSV50134455;