18-6868926-T-C

Position:

• chr18-6868926-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP28	NM_001366230.1	c.811+692T>C		intron_variant		ENST00000383472.9	NP_001353159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP28	ENST00000383472.9	c.811+692T>C		intron_variant		5	NM_001366230.1	ENSP00000372964	A2

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.848

Alfa AF: 0.895 Hom.: 79765

Bravo AF: 0.848

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.65

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: rs2567261; hg19: chr18-6868925;