rs1440611788

Variant names:

• chr1-3463209-C-G
• rs1440611788
• NM_014448.4:c.125C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-3463209-C-G
• chr1-3463209-C-T

Variant summary

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

The NM_014448.4(ARHGEF16):​c.125C>G​(p.Pro42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,393,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P42L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ARHGEF16 NM_014448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 5 publications found

Genes affected

ARHGEF16 (HGNC:15515): (Rho guanine nucleotide exchange factor 16) Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

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=0.049541116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014448.4. 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
	ARHGEF16	NM_014448.4	MANE Select	c.125C>G	p.Pro42Arg	missense	Exon 2 of 15	NP_055263.2	Q5VV41-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF16	ENST00000378378.9	TSL:2 MANE Select	c.125C>G	p.Pro42Arg	missense	Exon 2 of 15	ENSP00000367629.4	Q5VV41-1
	ARHGEF16	ENST00000868563.1		c.125C>G	p.Pro42Arg	missense	Exon 2 of 17	ENSP00000538622.1
	ARHGEF16	ENST00000868561.1		c.125C>G	p.Pro42Arg	missense	Exon 2 of 15	ENSP00000538620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1393768 Hom.: 0 Cov.: 31 AF XY: 0.00000437 AC XY: 3 AN XY: 686642

African (AFR) AF: 0.00 AC: 0 AN: 31502

American (AMR) AF: 0.00 AC: 0 AN: 35470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35622

South Asian (SAS) AF: 0.00 AC: 0 AN: 78994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1075842

Other (OTH) AF: 0.0000173 AC: 1 AN: 57746

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.9
DANN	Benign	0.81
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.038
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.070
Sift	Benign	0.048	D
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.047
MutPred		0.22		Gain of MoRF binding (P = 0.0016)
MVP		0.076
MPC		0.25
ClinPred		0.069	T
GERP RS		1.9
Varity_R		0.052
gMVP		0.33
Mutation Taster		=97/3	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: rs1440611788; hg19: chr1-3379773;