rs3809828

Variant names:

• chr17-7343532-C-T
• rs3809828
• NM_014716.4:c.498C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014716.4(ACAP1):​c.498C>T​(p.Tyr166Tyr) 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP1	NM_014716.4	MANE Select	c.498C>T	p.Tyr166Tyr	synonymous	Exon 6 of 22	NP_055531.1	Q15027

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAP1	ENST00000158762.8	TSL:1 MANE Select	c.498C>T	p.Tyr166Tyr	synonymous	Exon 6 of 22	ENSP00000158762.3	Q15027
	ACAP1	ENST00000911039.1		c.498C>T	p.Tyr166Tyr	synonymous	Exon 6 of 22	ENSP00000581098.1
	ACAP1	ENST00000911040.1		c.498C>T	p.Tyr166Tyr	synonymous	Exon 6 of 22	ENSP00000581099.1

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

GnomAD2 exomes AF: 0.0644 AC: 16136 AN: 250410 AF XY: 0.0635

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 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

African (AFR) AF: 0.00786 AC: 263 AN: 33480

American (AMR) AF: 0.0470 AC: 2101 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 846 AN: 26114

East Asian (EAS) AF: 0.135 AC: 5351 AN: 39698

South Asian (SAS) AF: 0.0483 AC: 4165 AN: 86230

European-Finnish (FIN) AF: 0.100 AC: 5337 AN: 53354

Middle Eastern (MID) AF: 0.0392 AC: 226 AN: 5760

European-Non Finnish (NFE) AF: 0.0556 AC: 61836 AN: 1111756

Other (OTH) AF: 0.0562 AC: 3394 AN: 60368

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

African (AFR) AF: 0.00982 AC: 408 AN: 41544

American (AMR) AF: 0.0440 AC: 673 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3472

East Asian (EAS) AF: 0.141 AC: 729 AN: 5154

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4828

European-Finnish (FIN) AF: 0.0990 AC: 1050 AN: 10606

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0635 AC: 4319 AN: 67992

Other (OTH) AF: 0.0550 AC: 116 AN: 2108

Alfa AF: 0.0551 Hom.: 537

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.43
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3809828; hg19: chr17-7246851; COSMIC: COSV50134455; COSMIC: COSV50134455;