rs2052089

Variant names:

• chr7-66664967-T-C
• rs2052089
• ENST00000503687.2:n.397+26038T>C

Variant summary

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

The NM_001367741.1(RABGEF1):​c.-18+10341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,182 control chromosomes in the GnomAD database, including 44,585 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 0.76 (44585 hom., cov: 33)
• Consequence: RABGEF1 NM_001367741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 2 publications found

Genes affected

ENSG00000284461 (HGNC:):

RABGEF1 (HGNC:17676): (RAB guanine nucleotide exchange factor 1) RABGEF1 forms a complex with rabaptin-5 (RABPT5; MIM 603616) that is required for endocytic membrane fusion, and it serves as a specific guanine nucleotide exchange factor (GEF) for RAB5 (RAB5A; MIM 179512) (Horiuchi et al., 1997 [PubMed 9323142]).[supplied by OMIM, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367741.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGEF1	NM_001367741.1		c.-18+10341T>C		intron	N/A	NP_001354670.1
	RABGEF1	NM_001367737.1		c.-99+10341T>C		intron	N/A	NP_001354666.1
	RABGEF1	NM_001367725.1		c.-157+10341T>C		intron	N/A	NP_001354654.1	Q9UJ41-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284461	ENST00000503687.2	TSL:2	n.397+26038T>C		intron	N/A	ENSP00000421074.1	E9PHB8
	ENSG00000226824	ENST00000428557.1	TSL:3	n.42-3797T>C		intron	N/A
	ENSG00000226824	ENST00000439360.5	TSL:3	n.77-2431T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116157 AN: 152064 Hom.: 44540 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.764 AC: 116263 AN: 152182 Hom.: 44585 Cov.: 33 AF XY: 0.768 AC XY: 57117 AN XY: 74404

African (AFR) AF: 0.823 AC: 34195 AN: 41540

American (AMR) AF: 0.801 AC: 12250 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2722 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3569 AN: 5156

South Asian (SAS) AF: 0.708 AC: 3417 AN: 4824

European-Finnish (FIN) AF: 0.757 AC: 8018 AN: 10588

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49624 AN: 67992

Other (OTH) AF: 0.770 AC: 1627 AN: 2114

Alfa AF: 0.754 Hom.: 5617

Bravo AF: 0.770

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2052089; hg19: chr7-66129954;