chr4-148066821-T-C

Variant names:

• chr4-148066821-T-C
• rs7660368
• NM_024605.4:c.2272+2314T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024605.4(ARHGAP10):​c.2272+2314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,114 control chromosomes in the GnomAD database, including 22,949 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22949 hom., cov: 33)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 11 publications found

Genes affected

ARHGAP10 (HGNC:26099): (Rho GTPase activating protein 10) Predicted to enable GTPase activator activity. Predicted to be involved in cytoskeleton organization and negative regulation of apoptotic process. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024605.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP10	NM_024605.4	MANE Select	c.2272+2314T>C		intron	N/A	NP_078881.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP10	ENST00000336498.8	TSL:1 MANE Select	c.2272+2314T>C		intron	N/A	ENSP00000336923.3
	ARHGAP10	ENST00000506020.5	TSL:1	n.1347+2314T>C		intron	N/A
	ARHGAP10	ENST00000506054.5	TSL:1	n.7404+2314T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79314 AN: 151996 Hom.: 22938 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.522 AC: 79348 AN: 152114 Hom.: 22949 Cov.: 33 AF XY: 0.529 AC XY: 39329 AN XY: 74362

African (AFR) AF: 0.262 AC: 10860 AN: 41468

American (AMR) AF: 0.622 AC: 9504 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4310 AN: 5180

South Asian (SAS) AF: 0.629 AC: 3033 AN: 4824

European-Finnish (FIN) AF: 0.642 AC: 6797 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41083 AN: 67982

Other (OTH) AF: 0.517 AC: 1093 AN: 2114

Alfa AF: 0.579 Hom.: 111030

Bravo AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.44
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7660368; hg19: chr4-148987972;