18-6886548-T-C

Position:

• chr18-6886548-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001366230.1(ARHGAP28):​c.1454-609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,164 control chromosomes in the GnomAD database, including 51,299 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 0.82 (51299 hom., cov: 33)
• Consequence: ARHGAP28 NM_001366230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP28	NM_001366230.1	c.1454-609T>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.1454-609T>C		intron_variant		5	NM_001366230.1	ENSP00000372964	A2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124609 AN: 152046 Hom.: 51269 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.819 AC: 124689 AN: 152164 Hom.: 51299 Cov.: 33 AF XY: 0.814 AC XY: 60578 AN XY: 74382

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.807

Alfa AF: 0.852 Hom.: 92057

Bravo AF: 0.814

Asia WGS AF: 0.688 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 34

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

Publications

LitVar

Other links and lift over

dbSNP: rs686428; hg19: chr18-6886547;