chr8-130284521-A-C

Variant names:

• chr8-130284521-A-C
• rs4733781
• NM_018482.4:c.187-47527T>G

Variant summary

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

The NM_018482.4(ASAP1):​c.187-47527T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,830 control chromosomes in the GnomAD database, including 7,482 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 0.29 (7482 hom., cov: 30)
• Consequence: ASAP1 NM_018482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• Publications: 33 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018482.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAP1	NM_018482.4	MANE Select	c.187-47527T>G		intron	N/A	NP_060952.2
	ASAP1	NM_001362924.1		c.187-47527T>G		intron	N/A	NP_001349853.1
	ASAP1	NM_001247996.2		c.166-47527T>G		intron	N/A	NP_001234925.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAP1	ENST00000518721.6	TSL:5 MANE Select	c.187-47527T>G		intron	N/A	ENSP00000429900.1
	ASAP1	ENST00000521075.5	TSL:1	n.*169-47527T>G		intron	N/A	ENSP00000428463.1
	ASAP1	ENST00000357668.2	TSL:5	c.166-47527T>G		intron	N/A	ENSP00000350297.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44754 AN: 151712 Hom.: 7482 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.295 AC: 44773 AN: 151830 Hom.: 7482 Cov.: 30 AF XY: 0.303 AC XY: 22511 AN XY: 74178

African (AFR) AF: 0.155 AC: 6424 AN: 41436

American (AMR) AF: 0.336 AC: 5129 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1388 AN: 3462

East Asian (EAS) AF: 0.586 AC: 2999 AN: 5116

South Asian (SAS) AF: 0.517 AC: 2479 AN: 4794

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10530

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21735 AN: 67914

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.315 Hom.: 12764

Bravo AF: 0.289

Asia WGS AF: 0.467 AC: 1626 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		0.75
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: rs4733781; hg19: chr8-131296767;