dbSNP rs3809828: ACAP1:p.Tyr166Tyr (chr17-7343532-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

14 publications found

Variant links:

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]

ACAP1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAP1	NM_014716.4 link	c.498C>T	p.Tyr166Tyr	synonymous_variant	Exon 6 of 22	ENST00000158762.8	NP_055531.1	Q15027
ACAP1	XM_047437150.1 link	c.276C>T	p.Tyr92Tyr	synonymous_variant	Exon 6 of 22		XP_047293106.1
ACAP1	XM_047437151.1 link	c.276C>T	p.Tyr92Tyr	synonymous_variant	Exon 5 of 21		XP_047293107.1
ACAP1	XM_047437152.1 link	c.498C>T	p.Tyr166Tyr	synonymous_variant	Exon 6 of 18		XP_047293108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAP1	ENST00000158762.8 link	c.498C>T	p.Tyr166Tyr	synonymous_variant	Exon 6 of 22	1	NM_014716.4	ENSP00000158762.3		Q15027

Frequencies

GnomAD3 genomes

AF:

0.0504

AC:

7664

AN:

152078

Hom.:

292

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0567

AC XY:

41239

AN XY:

727010

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4748

9496

14244

18992

23740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2218

4436

6654

8872

11090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0504

AC:

7671

AN:

152196

Hom.:

292

Cov.:

AF XY:

0.0519

AC XY:

3860

AN XY:

74414

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.0635

AC:

4319

AN:

67992

Other (OTH)

AF:

0.0550

AC:

116

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

372

743

1115

1486

1858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.43

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over