10-24650736-T-C

Variant names:

• chr10-24650736-T-C
• rs4147179
• NM_020824.4:c.269-15633A>G

Variant summary

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

The NM_001367450.1(ARHGAP21):​c.-178A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,992 control chromosomes in the GnomAD database, including 21,365 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 0.53 (21365 hom., cov: 32)
• Consequence: ARHGAP21 NM_001367450.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 6 publications found

Genes affected

ARHGAP21 (HGNC:23725): (Rho GTPase activating protein 21) ARHGAP21 functions preferentially as a GTPase-activating protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3 complex (MIM 604221) and F-actin dynamics at the Golgi through control of CDC42 activity (Dubois et al., 2005 [PubMed 15793564]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367450.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP21	NM_020824.4	MANE Select	c.269-15633A>G		intron	N/A	NP_065875.3	Q5T5U3-1
	ARHGAP21	NM_001367450.1		c.-178A>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 28	NP_001354379.1
	ARHGAP21	NM_001367450.1		c.-178A>G		5_prime_UTR	Exon 5 of 28	NP_001354379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP21	ENST00000396432.7	TSL:1 MANE Select	c.269-15633A>G		intron	N/A	ENSP00000379709.2	Q5T5U3-1
	ARHGAP21	ENST00000446003.5	TSL:1	c.269-15633A>G		intron	N/A	ENSP00000405018.1	E7ESW5
	ARHGAP21	ENST00000958436.1		c.269-15633A>G		intron	N/A	ENSP00000628495.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80313 AN: 151874 Hom.: 21354 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.529 AC: 80361 AN: 151992 Hom.: 21365 Cov.: 32 AF XY: 0.526 AC XY: 39051 AN XY: 74270

African (AFR) AF: 0.549 AC: 22766 AN: 41438

American (AMR) AF: 0.502 AC: 7668 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2086 AN: 5160

South Asian (SAS) AF: 0.446 AC: 2154 AN: 4826

European-Finnish (FIN) AF: 0.535 AC: 5637 AN: 10534

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36279 AN: 67976

Other (OTH) AF: 0.498 AC: 1049 AN: 2108

Alfa AF: 0.527 Hom.: 11489

Bravo AF: 0.524

Asia WGS AF: 0.408 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4147179; hg19: chr10-24939665;