chr6-129695948-T-G

Variant names:

• chr6-129695948-T-G
• rs1476042
• NM_033515.3:c.113+14076A>C

Variant summary

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

The NM_033515.3(ARHGAP18):​c.113+14076A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,910 control chromosomes in the GnomAD database, including 37,273 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 0.69 (37273 hom., cov: 30)
• Consequence: ARHGAP18 NM_033515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 6 publications found

Genes affected

ARHGAP18 (HGNC:21035): (Rho GTPase activating protein 18) Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase mediated signal transduction. Located in cytosol; nuclear speck; and plasma membrane. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP18	NM_033515.3	c.113+14076A>C		intron_variant	Intron 1 of 14	ENST00000368149.3	NP_277050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP18	ENST00000368149.3	c.113+14076A>C		intron_variant	Intron 1 of 14	1	NM_033515.3	ENSP00000357131.2

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105339 AN: 151790 Hom.: 37248 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.694 AC: 105412 AN: 151910 Hom.: 37273 Cov.: 30 AF XY: 0.696 AC XY: 51678 AN XY: 74224

African (AFR) AF: 0.563 AC: 23297 AN: 41388

American (AMR) AF: 0.702 AC: 10727 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2717 AN: 5150

South Asian (SAS) AF: 0.722 AC: 3474 AN: 4810

European-Finnish (FIN) AF: 0.798 AC: 8424 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52070 AN: 67950

Other (OTH) AF: 0.677 AC: 1429 AN: 2110

Alfa AF: 0.741 Hom.: 33315

Bravo AF: 0.680

Asia WGS AF: 0.624 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.91
DANN	Benign	0.48
PhyloP100		-0.60
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: rs1476042; hg19: chr6-130017093; COSMIC: COSV63763883;