chr8-130240512-A-G

Variant names:

• chr8-130240512-A-G
• rs10956514
• NM_018482.4:c.187-3518T>C

Variant summary

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

The NM_018482.4(ASAP1):​c.187-3518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,940 control chromosomes in the GnomAD database, including 11,361 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 0.38 (11361 hom., cov: 32)
• Consequence: ASAP1 NM_018482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 23 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]

ENSG00000287201 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAP1	NM_018482.4	c.187-3518T>C		intron_variant	Intron 3 of 29	ENST00000518721.6	NP_060952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAP1	ENST00000518721.6	c.187-3518T>C		intron_variant	Intron 3 of 29	5	NM_018482.4	ENSP00000429900.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57441 AN: 151822 Hom.: 11356 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.378 AC: 57465 AN: 151940 Hom.: 11361 Cov.: 32 AF XY: 0.383 AC XY: 28470 AN XY: 74258

African (AFR) AF: 0.277 AC: 11482 AN: 41452

American (AMR) AF: 0.413 AC: 6293 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1593 AN: 3468

East Asian (EAS) AF: 0.589 AC: 3030 AN: 5146

South Asian (SAS) AF: 0.558 AC: 2689 AN: 4818

European-Finnish (FIN) AF: 0.376 AC: 3962 AN: 10550

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27129 AN: 67940

Other (OTH) AF: 0.427 AC: 902 AN: 2110

Alfa AF: 0.403 Hom.: 15234

Bravo AF: 0.378

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.84
PhyloP100		-0.10
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: rs10956514; hg19: chr8-131252758; COSMIC: COSV63050129; COSMIC: COSV63050129;