rs8327

Variant names:

• chr17-45395141-A-G
• rs8327
• NM_001282290.2:c.*315T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282290.2(ARHGAP27):​c.*315T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 413,192 control chromosomes in the GnomAD database, including 15,069 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 (4464 hom., cov: 32)
  • Exomes 𝑓: 0.27 (10605 hom.)
• Consequence: ARHGAP27 NM_001282290.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP27	NM_001282290.2	c.*315T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000685559.1	NP_001269219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP27	ENST00000685559.1	c.*315T>C		3_prime_UTR_variant	Exon 20 of 20		NM_001282290.2	ENSP00000509127.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34520 AN: 151894 Hom.: 4466 Cov.: 32

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.275 AC: 71716 AN: 261180 Hom.: 10605 Cov.: 2 AF XY: 0.276 AC XY: 37602 AN XY: 136126

African (AFR) AF: 0.0947 AC: 684 AN: 7220

American (AMR) AF: 0.201 AC: 1670 AN: 8324

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2097 AN: 8386

East Asian (EAS) AF: 0.377 AC: 6198 AN: 16440

South Asian (SAS) AF: 0.289 AC: 7395 AN: 25572

European-Finnish (FIN) AF: 0.353 AC: 5929 AN: 16812

Middle Eastern (MID) AF: 0.306 AC: 375 AN: 1224

European-Non Finnish (NFE) AF: 0.268 AC: 43171 AN: 161308

Other (OTH) AF: 0.264 AC: 4197 AN: 15894

GnomAD4 genome AF: 0.227 AC: 34531 AN: 152012 Hom.: 4464 Cov.: 32 AF XY: 0.234 AC XY: 17348 AN XY: 74270

African (AFR) AF: 0.0956 AC: 3967 AN: 41480

American (AMR) AF: 0.216 AC: 3305 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 854 AN: 3462

East Asian (EAS) AF: 0.351 AC: 1808 AN: 5146

South Asian (SAS) AF: 0.307 AC: 1481 AN: 4822

European-Finnish (FIN) AF: 0.354 AC: 3739 AN: 10564

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18564 AN: 67942

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.258 Hom.: 18465

Bravo AF: 0.211

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.29
PhyloP100		0.24
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: rs8327; hg19: chr17-43472507; COSMIC: COSV65359116; COSMIC: COSV65359116;