chr8-130080167-T-C

Variant names:

• chr8-130080167-T-C
• rs6984045
• NM_018482.4:c.2573-196A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018482.4(ASAP1):​c.2573-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,284 control chromosomes in the GnomAD database, including 70 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 0.027 (70 hom., cov: 32)
• Consequence: ASAP1 NM_018482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• Publications: 16 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=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0274 (4171/152284) while in subpopulation AFR AF = 0.0446 (1855/41556). AF 95% confidence interval is 0.0429. There are 70 homozygotes in GnomAd4. There are 1963 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4171 AD gene.

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.2573-196A>G		intron	N/A	NP_060952.2
	ASAP1	NM_001362924.1		c.2582-196A>G		intron	N/A	NP_001349853.1
	ASAP1	NM_001247996.2		c.2552-196A>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.2573-196A>G		intron	N/A	ENSP00000429900.1
	ASAP1	ENST00000524124.5	TSL:1	c.2033-196A>G		intron	N/A	ENSP00000429391.1
	ASAP1	ENST00000521075.5	TSL:1	n.*2555-196A>G		intron	N/A	ENSP00000428463.1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4170 AN: 152166 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0274 AC: 4171 AN: 152284 Hom.: 70 Cov.: 32 AF XY: 0.0264 AC XY: 1963 AN XY: 74470

African (AFR) AF: 0.0446 AC: 1855 AN: 41556

American (AMR) AF: 0.0198 AC: 303 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4830

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1695 AN: 68024

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0261 Hom.: 182

Bravo AF: 0.0300

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.46
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism

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: rs6984045; hg19: chr8-131092413;