rs12947718

Positions:

• chr17-45415735-G-A

Variant summary

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

The NM_001282290.2(ARHGAP27):​c.658-9652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,116 control chromosomes in the GnomAD database, including 1,711 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 0.14 (1711 hom., cov: 31)
• Consequence: ARHGAP27 NM_001282290.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

Genes affected

ARHGAP27 (HGNC:31813): (Rho GTPase activating protein 27) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may pay a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP27	NM_001282290.2	c.658-9652C>T		intron_variant		ENST00000685559.1	NP_001269219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP27	ENST00000685559.1	c.658-9652C>T		intron_variant			NM_001282290.2	ENSP00000509127

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20666 AN: 151998 Hom.: 1713 Cov.: 31

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.136 AC: 20665 AN: 152116 Hom.: 1711 Cov.: 31 AF XY: 0.128 AC XY: 9488 AN XY: 74366

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0606

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.182

Alfa AF: 0.176 Hom.: 1818

Bravo AF: 0.146

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.42

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: rs12947718; hg19: chr17-43493101;