4-148053451-T-C

Variant names:

• chr4-148053451-T-C
• rs6845865
• NM_024605.4:c.2027+6400T>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.2027+6400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,072 control chromosomes in the GnomAD database, including 6,717 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 0.26 (6717 hom., cov: 32)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 24 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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.2027+6400T>C		intron_variant	Intron 20 of 22	ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.2027+6400T>C		intron_variant	Intron 20 of 22	1	NM_024605.4	ENSP00000336923.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40154 AN: 151954 Hom.: 6688 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.265 AC: 40238 AN: 152072 Hom.: 6717 Cov.: 32 AF XY: 0.267 AC XY: 19871 AN XY: 74340

African (AFR) AF: 0.475 AC: 19689 AN: 41446

American (AMR) AF: 0.247 AC: 3781 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5164

South Asian (SAS) AF: 0.250 AC: 1200 AN: 4808

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10578

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10753 AN: 68004

Other (OTH) AF: 0.236 AC: 499 AN: 2112

Alfa AF: 0.195 Hom.: 11735

Bravo AF: 0.274

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		-0.65
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: rs6845865; hg19: chr4-148974602; COSMIC: COSV60600307;