chr7-66728196-T-C

Variant names:

• chr7-66728196-T-C
• rs17566701
• ENST00000503687.2:n.398-43687T>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.-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
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGEF1	NM_001367741.1		c.-17-43687T>C		intron	N/A	NP_001354670.1
	RABGEF1	NM_001367737.1		c.-18+27347T>C		intron	N/A	NP_001354666.1
	RABGEF1	NM_001367738.1		c.-18+27347T>C		intron	N/A	NP_001354667.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284461	ENST00000503687.2	TSL:2	n.398-43687T>C		intron	N/A	ENSP00000421074.1
	RABGEF1	ENST00000901856.1		c.-653-11961T>C		intron	N/A	ENSP00000571915.1
	RABGEF1	ENST00000901857.1		c.-212-40635T>C		intron	N/A	ENSP00000571916.1

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

African (AFR) AF: 0.741 AC: 30736 AN: 41478

American (AMR) AF: 0.564 AC: 8621 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2273 AN: 3472

East Asian (EAS) AF: 0.738 AC: 3782 AN: 5128

South Asian (SAS) AF: 0.658 AC: 3175 AN: 4824

European-Finnish (FIN) AF: 0.605 AC: 6388 AN: 10566

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36692 AN: 67946

Other (OTH) AF: 0.610 AC: 1290 AN: 2114

Alfa AF: 0.571 Hom.: 21618

Bravo AF: 0.620

Asia WGS AF: 0.709 AC: 2465 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	4.3
DANN	Benign	0.72
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs17566701; hg19: chr7-66193183;