19-7359642-A-T

Position:

• chr19-7359642-A-T

Variant summary

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

The NM_001367823.1(ARHGEF18):​c.-110-3139A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,162 control chromosomes in the GnomAD database, including 2,062 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 0.092 (2062 hom., cov: 31)
• Consequence: ARHGEF18 NM_001367823.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF18	NM_001367823.1	c.-110-3139A>T		intron_variant		ENST00000668164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF18	ENST00000668164.2	c.-110-3139A>T		intron_variant			NM_001367823.1	A2
ARHGEF18	ENST00000671891.2	c.86-3139A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13986 AN: 152044 Hom.: 2052 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0293

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00384

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0923 AC: 14037 AN: 152162 Hom.: 2062 Cov.: 31 AF XY: 0.0897 AC XY: 6671 AN XY: 74398

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00382

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.00692 Hom.: 37

Bravo AF: 0.107

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs6603109; hg19: chr19-7424528;