rs12947718

Variant names:

• chr17-45415735-G-A
• rs12947718
• NM_001282290.2:c.658-9652C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARHGAP27	NM_001282290.2	c.658-9652C>T		intron_variant	Intron 4 of 19	ENST00000685559.1	NP_001269219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP27	ENST00000685559.1	c.658-9652C>T		intron_variant	Intron 4 of 19		NM_001282290.2	ENSP00000509127.1

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

African (AFR) AF: 0.0838 AC: 3475 AN: 41488

American (AMR) AF: 0.172 AC: 2629 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0606 AC: 292 AN: 4818

European-Finnish (FIN) AF: 0.0416 AC: 441 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12311 AN: 67992

Other (OTH) AF: 0.182 AC: 382 AN: 2104

Alfa AF: 0.165 Hom.: 3259

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
PhyloP100		-0.039
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: rs12947718; hg19: chr17-43493101;