ENST00000503687.2:n.397+48654G>C

Variant names:

• chr7-66687052-A-C
• rs1584631345
• ENST00000503687.2:n.397+48123A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000503687.2(ENSG00000284461):​n.397+48123A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: ENSG00000284461 ENST00000503687.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503687.2. 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+32426A>C		intron	N/A	NP_001354670.1
	RABGEF1	NM_001367737.1		c.-98-13717A>C		intron	N/A	NP_001354666.1
	RABGEF1	NM_001367738.1		c.-99+4794A>C		intron	N/A	NP_001354667.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284461	ENST00000503687.2	TSL:2	n.397+48123A>C		intron	N/A	ENSP00000421074.1	E9PHB8
	RABGEF1	ENST00000901856.1		c.-654+4794A>C		intron	N/A	ENSP00000571915.1
	RABGEF1	ENST00000901857.1		c.-213+4794A>C		intron	N/A	ENSP00000571916.1

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.77

Splicing

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

Other links and lift over

dbSNP: rs1584631345; hg19: chr7-66152039;