17-8313079-T-C

Variant names:

• chr17-8313079-T-C
• rs1060503817
• NM_173728.4:c.759T>C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_173728.4(ARHGEF15):​c.759T>C​(p.Pro253Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF15 NM_173728.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-8313079-T-C is Benign according to our data. Variant chr17-8313079-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 412669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.009 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.759T>C	p.Pro253Pro	synonymous_variant	Exon 3 of 16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.759T>C	p.Pro253Pro	synonymous_variant	Exon 3 of 16	1	NM_173728.4	ENSP00000355026.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 108 AN: 82946 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00207

Gnomad AMR AF: 0.00117

Gnomad ASJ AF: 0.000919

Gnomad EAS AF: 0.000335

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.00174

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00517 AC: 4307 AN: 833250 Hom.: 0 Cov.: 34 AF XY: 0.00490 AC XY: 2070 AN XY: 422716

Gnomad4 AFR exome AF: 0.00993

Gnomad4 AMR exome AF: 0.0510

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.000384

Gnomad4 SAS exome AF: 0.00616

Gnomad4 FIN exome AF: 0.00702

Gnomad4 NFE exome AF: 0.00174

Gnomad4 OTH exome AF: 0.00619

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00130 AC: 108 AN: 82980 Hom.: 0 Cov.: 26 AF XY: 0.00133 AC XY: 53 AN XY: 39732

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00117

Gnomad4 ASJ AF: 0.000919

Gnomad4 EAS AF: 0.000336

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.00110

Gnomad4 NFE AF: 0.00152

Gnomad4 OTH AF: 0.00172

Alfa AF: 0.0237 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Nov 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.7
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1060503817; hg19: chr17-8216397;