rs8100029

Variant names:

• chr19-7383946-A-G
• rs8100029
• NM_001367823.1:c.967+743A>G

Variant summary

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

The NM_001367823.1(ARHGEF18):​c.967+743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,962 control chromosomes in the GnomAD database, including 1,960 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 0.12 (1960 hom., cov: 31)
• Consequence: ARHGEF18 NM_001367823.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 6 publications found

Genes affected

ARHGEF18 (HGNC:17090): (Rho/Rac guanine nucleotide exchange factor 18) Rho GTPases are GTP binding proteins that regulate a wide spectrum of cellular functions. These cellular processes include cytoskeletal rearrangements, gene transcription, cell growth and motility. Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GEF family. Family members share a common feature, a Dbl (DH) homology domain followed by a pleckstrin (PH) homology domain. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2018]

ARHGEF18-AS1 (HGNC:55284): (ARHGEF18 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF18	NM_001367823.1	c.967+743A>G		intron_variant	Intron 10 of 28	ENST00000668164.2	NP_001354752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF18	ENST00000668164.2	c.967+743A>G		intron_variant	Intron 10 of 28		NM_001367823.1	ENSP00000499655.2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17618 AN: 151844 Hom.: 1957 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.116 AC: 17644 AN: 151962 Hom.: 1960 Cov.: 31 AF XY: 0.115 AC XY: 8577 AN XY: 74280

African (AFR) AF: 0.293 AC: 12102 AN: 41370

American (AMR) AF: 0.0649 AC: 990 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5174

South Asian (SAS) AF: 0.0831 AC: 400 AN: 4814

European-Finnish (FIN) AF: 0.0756 AC: 801 AN: 10590

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2722 AN: 67980

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0601 Hom.: 2270

Bravo AF: 0.122

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.59
PhyloP100		-0.52

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: rs8100029; hg19: chr19-7448832;