10-24650736-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020824.4(ARHGAP21):c.269-15633A>G variant causes a intron 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_020824.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP21	NM_020824.4	c.269-15633A>G		intron_variant		ENST00000396432.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP21	ENST00000396432.7	c.269-15633A>G		intron_variant		1	NM_020824.4	A2

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

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.498

Alfa AF: 0.528 Hom.: 10407

Bravo AF: 0.524

Asia WGS AF: 0.408 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs4147179; hg19: chr10-24939665;