7-66728196-T-C

Variant names:

• chr7-66728196-T-C
• rs17566701
• ENST00000503687.2:n.398-43687T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367741.1(RABGEF1):​c.-17-43687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,012 control chromosomes in the GnomAD database, including 29,573 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 0.62 (29573 hom., cov: 31)
• Consequence: RABGEF1 NM_001367741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGEF1	NM_001367741.1	c.-17-43687T>C		intron_variant	Intron 1 of 9		NP_001354670.1
RABGEF1	NM_001367737.1	c.-18+27347T>C		intron_variant	Intron 2 of 9		NP_001354666.1
RABGEF1	NM_001367738.1	c.-18+27347T>C		intron_variant	Intron 2 of 9		NP_001354667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284461	ENST00000503687.2	n.398-43687T>C		intron_variant	Intron 3 of 12	2		ENSP00000421074.1
RABGEF1	ENST00000607882.5	n.-814-11800T>C		intron_variant	Intron 2 of 9	2		ENSP00000476796.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93634 AN: 151894 Hom.: 29529 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.617 AC: 93736 AN: 152012 Hom.: 29573 Cov.: 31 AF XY: 0.618 AC XY: 45929 AN XY: 74278

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.610

Alfa AF: 0.564 Hom.: 12314

Bravo AF: 0.620

Asia WGS AF: 0.709 AC: 2465 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	4.3
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17566701; hg19: chr7-66193183;