rs1230103

Variant names:

• chr17-45408425-G-A
• rs1230103
• NM_001282290.2:c.658-2342C>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.658-2342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,950 control chromosomes in the GnomAD database, including 9,346 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 0.35 (9344 hom., cov: 31)
  • Exomes 𝑓: 0.44 (2 hom.)
• Consequence: ARHGAP27 NM_001282290.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP27	NM_001282290.2	c.658-2342C>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.658-2342C>T		intron_variant	Intron 4 of 19		NM_001282290.2	ENSP00000509127.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52403 AN: 151816 Hom.: 9332 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.438 AC: 7 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.600 AC: 6 AN: 10

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.345 AC: 52459 AN: 151934 Hom.: 9344 Cov.: 31 AF XY: 0.349 AC XY: 25955 AN XY: 74268

African (AFR) AF: 0.382 AC: 15813 AN: 41440

American (AMR) AF: 0.356 AC: 5432 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3464

East Asian (EAS) AF: 0.544 AC: 2807 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1768 AN: 4808

European-Finnish (FIN) AF: 0.337 AC: 3556 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20751 AN: 67922

Other (OTH) AF: 0.366 AC: 772 AN: 2112

Alfa AF: 0.319 Hom.: 13697

Bravo AF: 0.352

Asia WGS AF: 0.458 AC: 1588 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.24
PhyloP100		-0.12
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: rs1230103; hg19: chr17-43485791;