rs6506440

chr18-6781017-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366230.1(ARHGAP28):c.123-43745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,108 control chromosomes in the GnomAD database, including 5,312 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 0.19 (5312 hom., cov: 32)
• Consequence: ARHGAP28 NM_001366230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP28	NM_001366230.1	c.123-43745G>A		intron_variant		ENST00000383472.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP28	ENST00000383472.9	c.123-43745G>A		intron_variant		5	NM_001366230.1	A2
ARHGAP28	ENST00000532723.5	c.-35+1981G>A		intron_variant		3
ARHGAP28	ENST00000583410.1	c.17+26202G>A		intron_variant		5
ARHGAP28	ENST00000584387.1	c.42-43745G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29491 AN: 151990 Hom.: 5292 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.194 AC: 29552 AN: 152108 Hom.: 5312 Cov.: 32 AF XY: 0.193 AC XY: 14345 AN XY: 74380

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.177

Alfa AF: 0.0772 Hom.: 1878

Bravo AF: 0.212

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.1
Dann	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6506440; hg19: chr18-6781016; COSMIC: COSV67306855;