chr4-85570386-CTTT-C

Position:

• chr4-85570386-CTTT-C

Variant summary

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

The NM_001025616.3(ARHGAP24):​c.-20-135_-20-133del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 33,852 control chromosomes in the GnomAD database, including 6,252 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (102 hom., cov: 0)
  • Exomes 𝑓: 0.58 (6150 hom.)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

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 4-85570386-CTTT-C is Benign according to our data. Variant chr4-85570386-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 1235243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-135_-20-133del		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-20-135_-20-133del		intron_variant		2	NM_001025616.3	ENSP00000378611	P1
ARHGAP24	ENST00000503995.5	c.-20-135_-20-133del		intron_variant		1		ENSP00000423206
ARHGAP24	ENST00000505856.1	n.75-135_75-133del		intron_variant, non_coding_transcript_variant		2
ARHGAP24	ENST00000506421.5	n.118-135_118-133del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 1978 AN: 11416 Hom.: 102 Cov.: 0

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0154

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.580 AC: 12991 AN: 22412 Hom.: 6150 AF XY: 0.545 AC XY: 6640 AN XY: 12174

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.173 AC: 1982 AN: 11440 Hom.: 102 Cov.: 0 AF XY: 0.155 AC XY: 898 AN XY: 5780

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.0811

Gnomad4 ASJ AF: 0.0154

Gnomad4 EAS AF: 0.0161

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.109

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

Mar 15, 2020

- -

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: rs1560536758; hg19: chr4-86491539;