rs868188

Variant names:

• chr1-156937323-T-A
• rs868188
• NM_198236.3:c.4366A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-156937323-T-A
• chr1-156937323-T-C

Variant summary

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

The NM_198236.3(ARHGEF11):​c.4366A>T​(p.Ser1456Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1456G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARHGEF11 NM_198236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 28 publications found

Genes affected

ARHGEF11 (HGNC:14580): (Rho guanine nucleotide exchange factor 11) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. A similar protein in rat interacts with glutamate transporter EAAT4 and modulates its glutamate transport activity. Expression of the rat protein induces the reorganization of the actin cytoskeleton and its overexpression induces the formation of membrane ruffling and filopodia. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

LRRC71 (HGNC:26556): (leucine rich repeat containing 71)

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=0.28803933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198236.3. 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
	ARHGEF11	NM_198236.3	MANE Select	c.4366A>T	p.Ser1456Cys	missense	Exon 39 of 41	NP_937879.1	O15085-2
	ARHGEF11	NM_001377418.1		c.4357A>T	p.Ser1453Cys	missense	Exon 39 of 41	NP_001364347.1
	ARHGEF11	NM_001377419.1		c.4336A>T	p.Ser1446Cys	missense	Exon 38 of 40	NP_001364348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF11	ENST00000368194.8	TSL:1 MANE Select	c.4366A>T	p.Ser1456Cys	missense	Exon 39 of 41	ENSP00000357177.3	O15085-2
	ARHGEF11	ENST00000361409.2	TSL:1	c.4246A>T	p.Ser1416Cys	missense	Exon 38 of 40	ENSP00000354644.2	O15085-1
	ARHGEF11	ENST00000715594.1		c.4414A>T	p.Ser1472Cys	missense	Exon 41 of 43	ENSP00000520488.1	A0AAQ5BIK5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.25		Gain of catalytic residue at L1417 (P = 0.0118)
MVP		0.78
MPC		0.20
ClinPred		0.77	D
GERP RS		0.50
Varity_R		0.19
gMVP		0.27
Mutation Taster		=88/12	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: rs868188; hg19: chr1-156907115; COSMIC: COSV59355456; COSMIC: COSV59355456;