chr4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C

Position:

• chr4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001025616.3(ARHGAP24):​c.-20-160_-20-125del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0085 (17 hom., cov: 0)
• Consequence: ARHGAP24 NM_001025616.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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 4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is Benign according to our data. Variant chr4-85570360-CTTTCTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1800575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1115/131604) while in subpopulation AFR AF= 0.0279 (1011/36190). AF 95% confidence interval is 0.0265. There are 17 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3	c.-20-160_-20-125del		intron_variant		ENST00000395184.6	NP_001020787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6	c.-20-160_-20-125del		intron_variant		2	NM_001025616.3	ENSP00000378611	P1
ARHGAP24	ENST00000503995.5	c.-20-160_-20-125del		intron_variant		1		ENSP00000423206
ARHGAP24	ENST00000505856.1	n.75-160_75-125del		intron_variant, non_coding_transcript_variant		2
ARHGAP24	ENST00000506421.5	n.118-160_118-125del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1112 AN: 131524 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.0125

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.000515

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00365

Gnomad NFE AF: 0.000298

Gnomad OTH AF: 0.00913

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

GnomAD4 genome AF: 0.00847 AC: 1115 AN: 131604 Hom.: 17 Cov.: 0 AF XY: 0.00793 AC XY: 504 AN XY: 63582

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.0125

Gnomad4 EAS AF: 0.000213

Gnomad4 SAS AF: 0.000517

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000298

Gnomad4 OTH AF: 0.00903

Alfa AF: 0.00573 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879696923; hg19: chr4-86491513;