rs12640411

Positions:

• chr4-85648522-C-T

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.181-73363C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,732 control chromosomes in the GnomAD database, including 9,159 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 0.33 (9159 hom., cov: 32)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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]

LOC105377319 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.181-73363C>T		intron_variant		ENST00000395184.6	NP_001020787.2
LOC105377319	XR_007058168.1	n.4006+1012C>T		intron_variant, non_coding_transcript_variant
LOC105377319	XR_938955.4	n.4006+1012C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.181-73363C>T		intron_variant		2	NM_001025616.3	ENSP00000378611	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49370 AN: 151614 Hom.: 9137 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.326 AC: 49441 AN: 151732 Hom.: 9159 Cov.: 32 AF XY: 0.334 AC XY: 24778 AN XY: 74154

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.339

Alfa AF: 0.309 Hom.: 1411

Bravo AF: 0.336

Asia WGS AF: 0.595 AC: 2067 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.40

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: rs12640411; hg19: chr4-86569675;