9-131705224-C-T

Variant names:

• chr9-131705224-C-T
• rs7853122
• NM_001377935.1:c.61+34546G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377935.1(RAPGEF1):​c.61+34546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,220 control chromosomes in the GnomAD database, including 57,907 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 0.87 (57907 hom., cov: 32)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.61+34546G>A		intron_variant	Intron 1 of 26	ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.61+34546G>A		intron_variant	Intron 1 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.10+32181G>A		intron_variant	Intron 1 of 23	1		ENSP00000361263.2

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132339 AN: 152102 Hom.: 57846 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.870 AC: 132457 AN: 152220 Hom.: 57907 Cov.: 32 AF XY: 0.875 AC XY: 65112 AN XY: 74410

African (AFR) AF: 0.947 AC: 39346 AN: 41560

American (AMR) AF: 0.825 AC: 12621 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2875 AN: 3472

East Asian (EAS) AF: 0.843 AC: 4355 AN: 5166

South Asian (SAS) AF: 0.822 AC: 3967 AN: 4824

European-Finnish (FIN) AF: 0.926 AC: 9812 AN: 10594

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56680 AN: 67992

Other (OTH) AF: 0.844 AC: 1785 AN: 2114

Alfa AF: 0.853 Hom.: 10798

Bravo AF: 0.864

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.054
DANN	Benign	0.40
PhyloP100		-1.1
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: rs7853122; hg19: chr9-134580611;