11-128965057-C-T

Variant names:

• chr11-128965057-C-T
• rs2298599
• NM_001378024.1:c.*3850G>A

Variant summary

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

The NM_001378024.1(ARHGAP32):​c.*3850G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,924 control chromosomes in the GnomAD database, including 8,024 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 0.32 (8024 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP32 NM_001378024.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 6 publications found

Genes affected

ARHGAP32 (HGNC:17399): (Rho GTPase activating protein 32) RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP32	NM_001378024.1	c.*3850G>A		downstream_gene_variant		ENST00000682385.1	NP_001364953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP32	ENST00000682385.1	c.*3850G>A		downstream_gene_variant			NM_001378024.1	ENSP00000507720.1
ARHGAP32	ENST00000310343.13	c.*3850G>A		downstream_gene_variant		1		ENSP00000310561.8

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48677 AN: 151806 Hom.: 8021 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.277

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.321 AC: 48693 AN: 151924 Hom.: 8024 Cov.: 32 AF XY: 0.322 AC XY: 23922 AN XY: 74230

African (AFR) AF: 0.282 AC: 11681 AN: 41408

American (AMR) AF: 0.243 AC: 3717 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1419 AN: 5172

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4812

European-Finnish (FIN) AF: 0.436 AC: 4594 AN: 10534

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24302 AN: 67944

Other (OTH) AF: 0.275 AC: 577 AN: 2100

Alfa AF: 0.330 Hom.: 13945

Bravo AF: 0.303

Asia WGS AF: 0.240 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.51
PhyloP100		1.4
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2298599; hg19: chr11-128834952;