rs2052089

Positions:

• chr7-66664967-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGEF1	NM_001367741.1	c.-18+10341T>C		intron_variant			NP_001354670.1
RABGEF1	NM_001367737.1	c.-99+10341T>C		intron_variant			NP_001354666.1
RABGEF1	NM_001367725.1	c.-157+10341T>C		intron_variant			NP_001354654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000284461	ENST00000503687.2	n.397+26038T>C		intron_variant		2		ENSP00000421074.1

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

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.770

Alfa AF: 0.751 Hom.: 5348

Bravo AF: 0.770

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2052089; hg19: chr7-66129954;