9-131638191-C-T

Variant names:

• chr9-131638191-C-T
• rs7047157
• NM_001377935.1:c.651+444G>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.651+444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,318 control chromosomes in the GnomAD database, including 56,682 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 0.86 (56682 hom., cov: 33)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.651+444G>A		intron_variant	Intron 5 of 26	ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.651+444G>A		intron_variant	Intron 5 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.600+444G>A		intron_variant	Intron 5 of 23	1		ENSP00000361263.2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 131060 AN: 152200 Hom.: 56623 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.861 AC: 131176 AN: 152318 Hom.: 56682 Cov.: 33 AF XY: 0.866 AC XY: 64503 AN XY: 74470

African (AFR) AF: 0.922 AC: 38340 AN: 41578

American (AMR) AF: 0.822 AC: 12570 AN: 15300

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

East Asian (EAS) AF: 0.844 AC: 4373 AN: 5184

South Asian (SAS) AF: 0.823 AC: 3974 AN: 4828

European-Finnish (FIN) AF: 0.917 AC: 9727 AN: 10606

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56531 AN: 68028

Other (OTH) AF: 0.838 AC: 1773 AN: 2116

Alfa AF: 0.835 Hom.: 24702

Bravo AF: 0.854

Asia WGS AF: 0.840 AC: 2922 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	0.0040
DANN	Benign	0.32
PhyloP100		-4.0
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: rs7047157; hg19: chr9-134513578;