chr18-6868926-T-C

Variant names:

• chr18-6868926-T-C
• rs2567261
• NM_001366230.1:c.811+692T>C

Variant summary

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

The NM_001366230.1(ARHGAP28):​c.811+692T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 151,988 control chromosomes in the GnomAD database, including 55,351 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 0.85 (55351 hom., cov: 30)
• Consequence: ARHGAP28 NM_001366230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 publications found

Genes affected

ARHGAP28 (HGNC:25509): (Rho GTPase activating protein 28) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of GTP binding activity; regulation of actin filament organization; and regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366230.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP28	NM_001366230.1	MANE Select	c.811+692T>C		intron	N/A	NP_001353159.1
	ARHGAP28	NM_001366231.1		c.811+692T>C		intron	N/A	NP_001353160.1
	ARHGAP28	NM_001410873.1		c.655+692T>C		intron	N/A	NP_001397802.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP28	ENST00000383472.9	TSL:5 MANE Select	c.811+692T>C		intron	N/A	ENSP00000372964.4
	ARHGAP28	ENST00000262227.7	TSL:1	c.655+692T>C		intron	N/A	ENSP00000262227.3
	ARHGAP28	ENST00000419673.6	TSL:1	c.334+692T>C		intron	N/A	ENSP00000392660.2

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129195 AN: 151870 Hom.: 55319 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.851 AC: 129278 AN: 151988 Hom.: 55351 Cov.: 30 AF XY: 0.846 AC XY: 62849 AN XY: 74288

African (AFR) AF: 0.780 AC: 32275 AN: 41400

American (AMR) AF: 0.836 AC: 12768 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3035 AN: 3470

East Asian (EAS) AF: 0.720 AC: 3708 AN: 5148

South Asian (SAS) AF: 0.709 AC: 3411 AN: 4812

European-Finnish (FIN) AF: 0.888 AC: 9382 AN: 10566

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61931 AN: 68000

Other (OTH) AF: 0.848 AC: 1786 AN: 2106

Alfa AF: 0.891 Hom.: 100028

Bravo AF: 0.848

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		-0.17
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: rs2567261; hg19: chr18-6868925;