7-22329059-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012294.5(RAPGEF5):c.232-11022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,118 control chromosomes in the GnomAD database, including 6,597 homozygotes. 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 0.29 (6597 hom., cov: 33)
• Consequence: RAPGEF5 NM_012294.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPGEF5	NM_012294.5	c.232-11022A>G		intron_variant		ENST00000665637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPGEF5	ENST00000665637.1	c.232-11022A>G		intron_variant			NM_012294.5	P1
RAPGEF5	ENST00000405243.1	c.232-11022A>G		intron_variant		1
RAPGEF5	ENST00000344041.10	c.-228-11022A>G		intron_variant		5
RAPGEF5	ENST00000471484.1	n.249-11022A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44281 AN: 152000 Hom.: 6601 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.291 AC: 44304 AN: 152118 Hom.: 6597 Cov.: 33 AF XY: 0.294 AC XY: 21897 AN XY: 74372

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.267

Alfa AF: 0.304 Hom.: 12114

Bravo AF: 0.286

Asia WGS AF: 0.317 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.0
Dann	Benign	0.64

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: rs1522280; hg19: chr7-22368678;