rs4719687

Variant names:

• chr7-22202917-T-A
• rs4719687
• NM_012294.5:c.997-8884A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-22202917-T-A
• chr7-22202917-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012294.5(RAPGEF5):​c.997-8884A>T 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAPGEF5 NM_012294.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 4 publications found

Genes affected

RAPGEF5 (HGNC:16862): (Rap guanine nucleotide exchange factor 5) Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF5	NM_012294.5	c.997-8884A>T		intron_variant	Intron 9 of 25	ENST00000665637.1	NP_036426.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF5	ENST00000665637.1	c.997-8884A>T		intron_variant	Intron 9 of 25		NM_012294.5	ENSP00000499535.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151934 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 215360 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125230

African (AFR) AF: 0.00 AC: 0 AN: 5514

American (AMR) AF: 0.00 AC: 0 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7154

East Asian (EAS) AF: 0.00 AC: 0 AN: 6446

South Asian (SAS) AF: 0.00 AC: 0 AN: 44176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 114378

Other (OTH) AF: 0.00 AC: 0 AN: 10044

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151934 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41326

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 98070

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.72
PhyloP100		-1.9

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: rs4719687; hg19: chr7-22242535;