4-85794159-G-T

Variant names:

• chr4-85794159-G-T
• rs7687906
• NM_001025616.3:c.268+72187G>T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.268+72187G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,164 control chromosomes in the GnomAD database, including 53,868 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 0.84 (53868 hom., cov: 31)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

Genes affected

ARHGAP24 (HGNC:25361): (Rho GTPase activating protein 24) This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.268+72187G>T		intron_variant	Intron 3 of 9	ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.268+72187G>T		intron_variant	Intron 3 of 9	2	NM_001025616.3	ENSP00000378611.1
ARHGAP24	ENST00000395183.6	c.-18+15194G>T		intron_variant	Intron 1 of 7	1		ENSP00000378610.2
ARHGAP24	ENST00000503995.5	c.268+72187G>T		intron_variant	Intron 3 of 5	1		ENSP00000423206.1
ARHGAP24	ENST00000512201.5	c.-18+72187G>T		intron_variant	Intron 3 of 4	4		ENSP00000426105.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127827 AN: 152046 Hom.: 53826 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.841 AC: 127927 AN: 152164 Hom.: 53868 Cov.: 31 AF XY: 0.837 AC XY: 62221 AN XY: 74380

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.846

Alfa AF: 0.850 Hom.: 42493

Bravo AF: 0.838

Asia WGS AF: 0.828 AC: 2870 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7687906; hg19: chr4-86715312;