13-111153917-C-G

Variant names:

• chr13-111153917-C-G
• rs779091507
• NM_001354046.2:c.178C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001354046.2(ARHGEF7):​c.178C>G​(p.Pro60Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,452,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ARHGEF7 NM_001354046.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69
• Publications: 0 publications found

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354046.2. 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
	ARHGEF7	NM_001354046.2	MANE Select	c.178C>G	p.Pro60Ala	missense	Exon 2 of 22	NP_001340975.1	A0A2R8YG42
	ARHGEF7	NM_001113511.2		c.178C>G	p.Pro60Ala	missense	Exon 2 of 20	NP_001106983.1	Q14155-4
	ARHGEF7	NM_001320852.1		c.178C>G	p.Pro60Ala	missense	Exon 2 of 21	NP_001307781.1	A0A8V8TQ72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF7	ENST00000646102.2	MANE Select	c.178C>G	p.Pro60Ala	missense	Exon 2 of 22	ENSP00000495631.1	A0A2R8YG42
	ARHGEF7	ENST00000375741.6	TSL:1	c.178C>G	p.Pro60Ala	missense	Exon 2 of 20	ENSP00000364893.2	Q14155-4
	ARHGEF7	ENST00000317133.9	TSL:1	c.178C>G	p.Pro60Ala	missense	Exon 2 of 19	ENSP00000325994.5	Q14155-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000214 AC: 5 AN: 233644 AF XY: 0.0000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000300

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452904 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723040

African (AFR) AF: 0.00 AC: 0 AN: 31758

American (AMR) AF: 0.00 AC: 0 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.000130 AC: 5 AN: 38390

South Asian (SAS) AF: 0.00 AC: 0 AN: 85632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109158

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D
Eigen	Benign	0.16
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.71
Sift	Benign	0.037	D
Sift4G	Uncertain	0.027	D
Polyphen		0.23	B
Vest4		0.52
MutPred		0.51		Loss of glycosylation at P60 (P = 0.0236)
MVP		0.89
MPC		0.67
ClinPred		0.70	D
GERP RS		3.3
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.35
Mutation Taster		=42/58	disease causing

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: rs779091507; hg19: chr13-111806264;