NM_001367823.1:c.625G>C

Variant names:

• chr19-7379147-G-C
• rs1970605801
• NM_001367823.1:c.625G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367823.1(ARHGEF18):​c.625G>C​(p.Glu209Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000185 in 1,080,342 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: ARHGEF18 NM_001367823.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2758698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367823.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF18	NM_001367823.1	MANE Select	c.625G>C	p.Glu209Gln	missense	Exon 7 of 29	NP_001354752.1	Q6ZSZ5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF18	ENST00000668164.2	MANE Select	c.625G>C	p.Glu209Gln	missense	Exon 7 of 29	ENSP00000499655.2	Q6ZSZ5-4
	ARHGEF18	ENST00000671891.2		c.820G>C	p.Glu274Gln	missense	Exon 7 of 10	ENSP00000500339.2	A0A5F9ZHI8
	ARHGEF18-AS1	ENST00000795305.1		n.205+11429C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1080342 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 510190

African (AFR) AF: 0.00 AC: 0 AN: 22982

American (AMR) AF: 0.00 AC: 0 AN: 8424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14386

East Asian (EAS) AF: 0.00 AC: 0 AN: 26526

South Asian (SAS) AF: 0.00 AC: 0 AN: 19496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2918

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 920370

Other (OTH) AF: 0.0000229 AC: 1 AN: 43688

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.28	T
PhyloP100		5.2
Sift4G	Benign	0.083	T
Vest4		0.45
MVP		0.35
GERP RS		4.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1970605801; hg19: chr19-7444033;