rs6506440

Variant names:

• chr18-6781017-G-A
• rs6506440
• NM_001366230.1:c.123-43745G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ARHGAP28	NM_001366230.1	c.123-43745G>A		intron_variant	Intron 1 of 17	ENST00000383472.9	NP_001353159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP28	ENST00000383472.9	c.123-43745G>A		intron_variant	Intron 1 of 17	5	NM_001366230.1	ENSP00000372964.4
ARHGAP28	ENST00000584387.1	c.42-43745G>A		intron_variant	Intron 1 of 3	5		ENSP00000462831.1
ARHGAP28	ENST00000532723.5	c.-35+1981G>A		intron_variant	Intron 2 of 3	3		ENSP00000433390.1
ARHGAP28	ENST00000583410.1	c.17+26202G>A		intron_variant	Intron 2 of 2	5		ENSP00000464141.1

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

African (AFR) AF: 0.468 AC: 19407 AN: 41454

American (AMR) AF: 0.154 AC: 2359 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1791 AN: 5172

South Asian (SAS) AF: 0.149 AC: 721 AN: 4824

European-Finnish (FIN) AF: 0.0667 AC: 707 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3683 AN: 67996

Other (OTH) AF: 0.177 AC: 372 AN: 2106

Alfa AF: 0.105 Hom.: 6576

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
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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