18-6886548-T-G

Variant names:

• chr18-6886548-T-G
• rs686428
• NM_001366230.1:c.1454-609T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366230.1(ARHGAP28):​c.1454-609T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ARHGAP28 NM_001366230.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366230.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP28	NM_001366230.1	MANE Select	c.1454-609T>G		intron	N/A	NP_001353159.1	Q9P2N2-1
	ARHGAP28	NM_001366231.1		c.1454-609T>G		intron	N/A	NP_001353160.1
	ARHGAP28	NM_001410873.1		c.1298-609T>G		intron	N/A	NP_001397802.1	Q9P2N2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP28	ENST00000383472.9	TSL:5 MANE Select	c.1454-609T>G		intron	N/A	ENSP00000372964.4	Q9P2N2-1
	ARHGAP28	ENST00000262227.7	TSL:1	c.1298-609T>G		intron	N/A	ENSP00000262227.3	Q9P2N2-2
	ARHGAP28	ENST00000419673.6	TSL:1	c.977-609T>G		intron	N/A	ENSP00000392660.2	Q9P2N2-5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.71
DANN	Benign	0.76
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: 34

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

Other links and lift over

dbSNP: rs686428; hg19: chr18-6886547;