7-144361448-A-G

Position:

• chr7-144361448-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000056217.10(ARHGEF5):​c.-12-1210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (2799 hom., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF5 ENST00000056217.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF5	NM_005435.4	c.-12-1210A>G		intron_variant		ENST00000056217.10	NP_005426.2
ARHGEF5	XM_017012623.3	c.-12-1210A>G		intron_variant			XP_016868112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF5	ENST00000056217.10	c.-12-1210A>G		intron_variant		1	NM_005435.4	ENSP00000056217	P1
ARHGEF5	ENST00000498580.5	c.-12-1210A>G		intron_variant		3		ENSP00000417979

Frequencies

GnomAD3 genomes AF: 0.00 AC: 52494 AN: 123914 Hom.: 2799 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.441

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.424 AC: 52537 AN: 124030 Hom.: 2799 Cov.: 21 AF XY: 0.421 AC XY: 25273 AN XY: 60064

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.418

Alfa AF: 0.263 Hom.: 181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.51

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: rs1208143; hg19: chr7-144058541;