9-131578589-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377935.1(RAPGEF1):c.*908C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,358 control chromosomes in the GnomAD database, including 6,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6733 hom., cov: 33)
  • Exomes 𝑓: 0.33 (13 hom.)
• Consequence: RAPGEF1 NM_001377935.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.287

Genes affected

RAPGEF1 (HGNC:4568): (Rap guanine nucleotide exchange factor 1) This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-131578589-G-A is Benign according to our data. Variant chr9-131578589-G-A is described in ClinVar as [Benign]. Clinvar id is 1274200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPGEF1	NM_001377935.1	c.*908C>T		3_prime_UTR_variant	27/27	ENST00000683357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.*908C>T		3_prime_UTR_variant	27/27		NM_001377935.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41705 AN: 152036 Hom.: 6731 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.332 AC: 67 AN: 202 Hom.: 13 Cov.: 0 AF XY: 0.311 AC XY: 46 AN XY: 148

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.274 AC: 41731 AN: 152156 Hom.: 6733 Cov.: 33 AF XY: 0.275 AC XY: 20427 AN XY: 74378

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.288

Alfa AF: 0.338 Hom.: 9049

Bravo AF: 0.251

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 28171541) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.95
Dann	Benign	0.48

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: rs3739497; hg19: chr9-134453976;