7-144361448-A-G

Variant names:

• chr7-144361448-A-G
• rs1208143
• NM_005435.4:c.-12-1210A>G

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000056217.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF5	NM_005435.4	MANE Select	c.-12-1210A>G		intron	N/A	NP_005426.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF5	ENST00000056217.10	TSL:1 MANE Select	c.-12-1210A>G		intron	N/A	ENSP00000056217.5
	ARHGEF5	ENST00000498580.5	TSL:3	c.-12-1210A>G		intron	N/A	ENSP00000417979.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 52494 AN: 123914 Hom.: 2799 Cov.: 21

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

African (AFR) AF: 0.412 AC: 13880 AN: 33650

American (AMR) AF: 0.422 AC: 5385 AN: 12768

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1254 AN: 2960

East Asian (EAS) AF: 0.426 AC: 1888 AN: 4436

South Asian (SAS) AF: 0.443 AC: 1789 AN: 4040

European-Finnish (FIN) AF: 0.356 AC: 2837 AN: 7964

Middle Eastern (MID) AF: 0.441 AC: 119 AN: 270

European-Non Finnish (NFE) AF: 0.438 AC: 24277 AN: 55458

Other (OTH) AF: 0.418 AC: 704 AN: 1686

Alfa AF: 0.263 Hom.: 181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.51
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs1208143; hg19: chr7-144058541;