8-130177997-C-T

Variant names:

• chr8-130177997-C-T
• rs11774633
• NM_018482.4:c.746+1267G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018482.4(ASAP1):​c.746+1267G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,044 control chromosomes in the GnomAD database, including 29,932 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 0.61 (29932 hom., cov: 32)
• Consequence: ASAP1 NM_018482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 7 publications found

Genes affected

ASAP1 (HGNC:2720): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 1) This gene encodes an ADP-ribosylation factor (ARF) GTPase-activating protein. The GTPase-activating activity is stimulated by phosphatidylinositol 4,5-biphosphate (PIP2), and is greater towards ARF1 and ARF5, and lesser for ARF6. This gene maybe involved in regulation of membrane trafficking and cytoskeleton remodeling. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAP1	NM_018482.4	c.746+1267G>A		intron_variant	Intron 9 of 29	ENST00000518721.6	NP_060952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAP1	ENST00000518721.6	c.746+1267G>A		intron_variant	Intron 9 of 29	5	NM_018482.4	ENSP00000429900.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92093 AN: 151928 Hom.: 29884 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.606 AC: 92184 AN: 152044 Hom.: 29932 Cov.: 32 AF XY: 0.605 AC XY: 44961 AN XY: 74324

African (AFR) AF: 0.860 AC: 35714 AN: 41510

American (AMR) AF: 0.549 AC: 8389 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1818 AN: 3466

East Asian (EAS) AF: 0.671 AC: 3464 AN: 5164

South Asian (SAS) AF: 0.624 AC: 3012 AN: 4824

European-Finnish (FIN) AF: 0.466 AC: 4905 AN: 10532

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32956 AN: 67954

Other (OTH) AF: 0.612 AC: 1293 AN: 2114

Alfa AF: 0.537 Hom.: 28492

Bravo AF: 0.625

Asia WGS AF: 0.605 AC: 2104 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.41
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11774633; hg19: chr8-131190243;