7-144363575-C-T

Variant summary

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

The NM_005435.4(ARHGEF5):c.906C>T(p.Asp302=) 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 0.00018 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00011 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF5 NM_005435.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.80

Genes affected

ARHGEF5 (HGNC:13209): (Rho guanine nucleotide exchange factor 5) Rho GTPases play a fundamental role in numerous cellular processes 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. This protein may be involved in the control of cytoskeletal organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-144363575-C-T is Benign according to our data. Variant chr7-144363575-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.8 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF5	NM_005435.4	c.906C>T	p.Asp302=	synonymous_variant	2/15	ENST00000056217.10
ARHGEF5	XM_017012623.3	c.906C>T	p.Asp302=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF5	ENST00000056217.10	c.906C>T	p.Asp302=	synonymous_variant	2/15	1	NM_005435.4	P1
ARHGEF5	ENST00000498580.5	c.184+722C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 25 AN: 139708 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000843

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000807

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000115 AC: 156 AN: 1361320 Hom.: 2 Cov.: 32 AF XY: 0.000100 AC XY: 68 AN XY: 679958

Gnomad4 AFR exome AF: 0.000125

Gnomad4 AMR exome AF: 0.000982

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000707

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.0000889

Gnomad4 OTH exome AF: 0.000105

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000179 AC: 25 AN: 139816 Hom.: 0 Cov.: 25 AF XY: 0.000191 AC XY: 13 AN XY: 67972

Gnomad4 AFR AF: 0.000184

Gnomad4 AMR AF: 0.000842

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.0000807

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000148 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

ARHGEF5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs543899386; hg19: chr7-144060668; COSMIC: COSV50207647; COSMIC: COSV50207647;