chr4-85570815-G-A

Position:

• chr4-85570815-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001025616.3(ARHGAP24):​c.180+94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,357,474 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (69 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (46 hom.)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.450

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-85570815-G-A is Benign according to our data. Variant chr4-85570815-G-A is described in ClinVar as [Benign]. Clinvar id is 1267166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.180+94G>A		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.180+94G>A		intron_variant		2	NM_001025616.3	ENSP00000378611	P1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2337 AN: 152136 Hom.: 69 Cov.: 31

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00158 AC: 1905 AN: 1205220 Hom.: 46 Cov.: 17 AF XY: 0.00133 AC XY: 806 AN XY: 607904

Gnomad4 AFR exome AF: 0.0548

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.000332

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000412

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.0154 AC: 2342 AN: 152254 Hom.: 69 Cov.: 31 AF XY: 0.0146 AC XY: 1084 AN XY: 74448

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00746 Hom.: 8

Bravo AF: 0.0174

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.32

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: rs113510981; hg19: chr4-86491968;