chr4-36191866-T-C

Position:

• chr4-36191866-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015230.4(ARAP2):​c.1557+1712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,988 control chromosomes in the GnomAD database, including 4,715 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 0.23 (4715 hom., cov: 30)
• Consequence: ARAP2 NM_015230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

Genes affected

ARAP2 (HGNC:16924): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2) The protein encoded by this gene contains ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology domains. The protein is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RHO-GAP domain and does not have RHO-GAP activity. The protein associates with focal adhesions and functions downstream of RhoA to regulate focal adhesion dynamics. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARAP2	NM_015230.4	c.1557+1712A>G		intron_variant		ENST00000303965.9	NP_056045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARAP2	ENST00000303965.9	c.1557+1712A>G		intron_variant		1	NM_015230.4	ENSP00000302895	P1
ARAP2	ENST00000508066.1	n.1888+1712A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34454 AN: 151870 Hom.: 4716 Cov.: 30

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0816

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.227 AC: 34453 AN: 151988 Hom.: 4715 Cov.: 30 AF XY: 0.224 AC XY: 16672 AN XY: 74308

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.234

Alfa AF: 0.286 Hom.: 3266

Bravo AF: 0.214

Asia WGS AF: 0.193 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs13120537; hg19: chr4-36193488;