chr4-85570431-C-CT

Position:

• chr4-85570431-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001025616.3(ARHGAP24):​c.-20-80dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 413,320 control chromosomes in the GnomAD database, including 14,483 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8056 hom., cov: 0)
  • Exomes 𝑓: 0.26 (6427 hom.)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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 -10 ACMG points.

• BP6: Variant 4-85570431-C-CT is Benign according to our data. Variant chr4-85570431-C-CT is described in ClinVar as [Benign]. Clinvar id is 1259699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-80dup		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-20-80dup		intron_variant		2	NM_001025616.3	ENSP00000378611	P1
ARHGAP24	ENST00000503995.5	c.-20-80dup		intron_variant		1		ENSP00000423206
ARHGAP24	ENST00000505856.1	n.75-80dup		intron_variant, non_coding_transcript_variant		2
ARHGAP24	ENST00000506421.5	n.118-80dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 40058 AN: 130666 Hom.: 8032 Cov.: 0

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.257 AC: 72595 AN: 282602 Hom.: 6427 AF XY: 0.257 AC XY: 37976 AN XY: 147640

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.307 AC: 40111 AN: 130718 Hom.: 8056 Cov.: 0 AF XY: 0.326 AC XY: 20029 AN XY: 61512

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.314

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

Dec 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs202209554; hg19: chr4-86491584;