13-111217879-C-T

Variant names:

• chr13-111217879-C-T
• rs41275140
• NM_001354046.2:c.669C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001354046.2(ARHGEF7):​c.669C>T​(p.Ser223Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,608,802 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (10 hom., cov: 33)
  • Exomes 𝑓: 0.011 (135 hom.)
• Consequence: ARHGEF7 NM_001354046.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002760
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.654
• Publications: 3 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 13-111217879-C-T is Benign according to our data. Variant chr13-111217879-C-T is described in ClinVar as Benign. ClinVar VariationId is 769399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.654 with no splicing effect.
• BS2: High AC in GnomAd4 at 1258 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.669C>T	p.Ser223Ser	splice_region synonymous	Exon 5 of 22	NP_001340975.1	A0A2R8YG42
	ARHGEF7	NM_001113511.2		c.732C>T	p.Ser244Ser	splice_region synonymous	Exon 6 of 20	NP_001106983.1	Q14155-4
	ARHGEF7	NM_001320852.1		c.669C>T	p.Ser223Ser	splice_region synonymous	Exon 5 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.669C>T	p.Ser223Ser	splice_region synonymous	Exon 5 of 22	ENSP00000495631.1	A0A2R8YG42
	ARHGEF7	ENST00000375741.6	TSL:1	c.732C>T	p.Ser244Ser	splice_region synonymous	Exon 6 of 20	ENSP00000364893.2	Q14155-4
	ARHGEF7	ENST00000317133.9	TSL:1	c.669C>T	p.Ser223Ser	splice_region synonymous	Exon 5 of 19	ENSP00000325994.5	Q14155-3

Frequencies

GnomAD3 genomes AF: 0.00827 AC: 1259 AN: 152226 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00887 AC: 2194 AN: 247320 AF XY: 0.00867

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.00795

GnomAD4 exome AF: 0.0110 AC: 15952 AN: 1456458 Hom.: 135 Cov.: 31 AF XY: 0.0107 AC XY: 7707 AN XY: 723526

African (AFR) AF: 0.00153 AC: 51 AN: 33390

American (AMR) AF: 0.00155 AC: 69 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00135 AC: 35 AN: 25968

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39524

South Asian (SAS) AF: 0.000466 AC: 40 AN: 85876

European-Finnish (FIN) AF: 0.0327 AC: 1745 AN: 53290

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5704

European-Non Finnish (NFE) AF: 0.0122 AC: 13493 AN: 1108040

Other (OTH) AF: 0.00858 AC: 516 AN: 60142

GnomAD4 genome AF: 0.00826 AC: 1258 AN: 152344 Hom.: 10 Cov.: 33 AF XY: 0.00890 AC XY: 663 AN XY: 74498

African (AFR) AF: 0.00202 AC: 84 AN: 41582

American (AMR) AF: 0.00105 AC: 16 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.0315 AC: 334 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0118 AC: 803 AN: 68032

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00963 Hom.: 32

Bravo AF: 0.00582

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.90
PhyloP100		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=254/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.13
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: rs41275140; hg19: chr13-111870226;