chr4-85570865-G-A

Position:

• chr4-85570865-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001025616.3(ARHGAP24):​c.180+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 925,530 control chromosomes in the GnomAD database, including 27,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3945 hom., cov: 32)
  • Exomes 𝑓: 0.19 (23774 hom.)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.748

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-85570865-G-A is Benign according to our data. Variant chr4-85570865-G-A is described in ClinVar as [Benign]. Clinvar id is 1272761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.180+144G>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+144G>A		intron_variant		2	NM_001025616.3	ENSP00000378611	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25878 AN: 151988 Hom.: 3927 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.194 AC: 150336 AN: 773424 Hom.: 23774 Cov.: 10 AF XY: 0.200 AC XY: 79212 AN XY: 396038

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.788

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.170 AC: 25916 AN: 152106 Hom.: 3945 Cov.: 32 AF XY: 0.183 AC XY: 13619 AN XY: 74324

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.198

Alfa AF: 0.147 Hom.: 462

Bravo AF: 0.180

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.73

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: rs17384463; hg19: chr4-86492018;