chr1-17587608-C-G

Variant names:

• chr1-17587608-C-G
• rs201247982
• NM_018125.4:c.186C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018125.4(ARHGEF10L):​c.186C>G​(p.Asp62Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ARHGEF10L NM_018125.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 0 publications found

Genes affected

ARHGEF10L (HGNC:25540): (Rho guanine nucleotide exchange factor 10 like) This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04556963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018125.4. 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
	ARHGEF10L	NM_018125.4	MANE Select	c.186C>G	p.Asp62Glu	missense	Exon 3 of 29	NP_060595.3
	ARHGEF10L	NM_001011722.2		c.186C>G	p.Asp62Glu	missense	Exon 2 of 27	NP_001011722.2	Q9HCE6-2
	ARHGEF10L	NM_001438939.1		c.186C>G	p.Asp62Glu	missense	Exon 3 of 27	NP_001425868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10L	ENST00000361221.8	TSL:1 MANE Select	c.186C>G	p.Asp62Glu	missense	Exon 3 of 29	ENSP00000355060.3	Q9HCE6-1
	ARHGEF10L	ENST00000375415.5	TSL:1	c.186C>G	p.Asp62Glu	missense	Exon 2 of 27	ENSP00000364564.1	Q9HCE6-2
	ARHGEF10L	ENST00000970707.1		c.186C>G	p.Asp62Glu	missense	Exon 3 of 29	ENSP00000640766.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250648 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461498 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727046

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.060
DANN	Benign	0.60
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-2.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.13
Sift	Benign	0.62	T
Sift4G	Benign	0.95	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.25		Loss of sheet (P = 0.1158)
MVP		0.14
MPC		0.050
ClinPred		0.028	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.057
Mutation Taster		=100/0	polymorphism

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: rs201247982; hg19: chr1-17914103;