rs6461639

Variant names:

• chr7-22147337-T-A
• rs6461639
• NM_012294.5:c.1885-318A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-22147337-T-A
• chr7-22147337-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012294.5(RAPGEF5):​c.1885-318A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RAPGEF5 NM_012294.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 6 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]

ENSG00000305201 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF5	NM_012294.5	c.1885-318A>T		intron_variant	Intron 18 of 25	ENST00000665637.1	NP_036426.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF5	ENST00000665637.1	c.1885-318A>T		intron_variant	Intron 18 of 25		NM_012294.5	ENSP00000499535.1
RAPGEF5	ENST00000401957.6	c.976-318A>T		intron_variant	Intron 8 of 15	1		ENSP00000384044.1
RAPGEF5	ENST00000344041.10	c.1426-318A>T		intron_variant	Intron 18 of 25	5		ENSP00000343656.6
ENSG00000305201	ENST00000809527.1	n.186-4309T>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 91443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-3.2

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: rs6461639; hg19: chr7-22186955;