18-6812510-G-T

Variant summary

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

The NM_001366230.1(ARHGAP28):c.123-12252G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,168 control chromosomes in the GnomAD database, including 807 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 0.091 (807 hom., cov: 32)
• Consequence: ARHGAP28 NM_001366230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP28	NM_001366230.1	c.123-12252G>T		intron_variant		ENST00000383472.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP28	ENST00000383472.9	c.123-12252G>T		intron_variant		5	NM_001366230.1	A2

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13917 AN: 152050 Hom.: 807 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0915 AC: 13921 AN: 152168 Hom.: 807 Cov.: 32 AF XY: 0.0941 AC XY: 7003 AN XY: 74384

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.103 Hom.: 514

Bravo AF: 0.0854

Asia WGS AF: 0.195 AC: 676 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	3.2
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1431381; hg19: chr18-6812509;