rs1376749

Positions:

• chr2-143209823-G-A

Variant summary

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

The NM_018460.4(ARHGAP15):​c.235-6561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,122 control chromosomes in the GnomAD database, including 2,424 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 0.17 (2424 hom., cov: 32)
• Consequence: ARHGAP15 NM_018460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP15	NM_018460.4	c.235-6561G>A		intron_variant		ENST00000295095.11	NP_060930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.235-6561G>A		intron_variant		1	NM_018460.4	ENSP00000295095	P1
ARHGAP15	ENST00000409869.5	c.235-6561G>A		intron_variant		5		ENSP00000386560
ARHGAP15	ENST00000460776.5	n.183-6561G>A		intron_variant, non_coding_transcript_variant		5
ARHGAP15	ENST00000552641.5	n.303-6561G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25941 AN: 152004 Hom.: 2416 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.171 AC: 25988 AN: 152122 Hom.: 2424 Cov.: 32 AF XY: 0.171 AC XY: 12717 AN XY: 74384

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.175

Alfa AF: 0.150 Hom.: 879

Bravo AF: 0.178

Asia WGS AF: 0.179 AC: 622 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.66

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: rs1376749; hg19: chr2-143967392;