4-85570281-T-C

Position:

• chr4-85570281-T-C

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.-20-241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,680 control chromosomes in the GnomAD database, including 37,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (37623 hom., cov: 28)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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=-0.9).
• BP6: Variant 4-85570281-T-C is Benign according to our data. Variant chr4-85570281-T-C is described in ClinVar as [Benign]. Clinvar id is 1234179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-241T>C		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-20-241T>C		intron_variant		2	NM_001025616.3	ENSP00000378611	P1
ARHGAP24	ENST00000503995.5	c.-20-241T>C		intron_variant		1		ENSP00000423206
ARHGAP24	ENST00000505856.1	n.75-241T>C		intron_variant, non_coding_transcript_variant		2
ARHGAP24	ENST00000506421.5	n.118-241T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101589 AN: 151560 Hom.: 37627 Cov.: 28

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.856

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.670 AC: 101592 AN: 151680 Hom.: 37623 Cov.: 28 AF XY: 0.662 AC XY: 49077 AN XY: 74112

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.688

Alfa AF: 0.764 Hom.: 5860

Bravo AF: 0.638

Asia WGS AF: 0.443 AC: 1537 AN: 3470

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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.35

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: rs1871823; hg19: chr4-86491434;