chr7-66688114-A-G

Variant names:

• chr7-66688114-A-G
• rs2659915
• ENST00000503687.2:n.397+49185A>G

Variant summary

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

The ENST00000503687.2(ENSG00000284461):​n.397+49185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 146,936 control chromosomes in the GnomAD database, including 19,316 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 0.50 (19316 hom., cov: 26)
• Consequence: ENSG00000284461 ENST00000503687.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGEF1	NM_001367741.1	c.-18+33488A>G		intron_variant	Intron 1 of 9		NP_001354670.1
RABGEF1	NM_001367737.1	c.-98-12655A>G		intron_variant	Intron 1 of 9		NP_001354666.1
RABGEF1	NM_001367738.1	c.-99+5856A>G		intron_variant	Intron 1 of 9		NP_001354667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284461	ENST00000503687.2	n.397+49185A>G		intron_variant	Intron 3 of 12	2		ENSP00000421074.1
RABGEF1	ENST00000607882.5	n.-873+5856A>G		intron_variant	Intron 1 of 9	2		ENSP00000476796.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 73332 AN: 146854 Hom.: 19313 Cov.: 26

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.499 AC: 73348 AN: 146936 Hom.: 19316 Cov.: 26 AF XY: 0.503 AC XY: 35685 AN XY: 70988

African (AFR) AF: 0.339 AC: 13462 AN: 39764

American (AMR) AF: 0.519 AC: 7543 AN: 14534

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2180 AN: 3458

East Asian (EAS) AF: 0.739 AC: 3706 AN: 5016

South Asian (SAS) AF: 0.644 AC: 3044 AN: 4730

European-Finnish (FIN) AF: 0.596 AC: 5273 AN: 8842

Middle Eastern (MID) AF: 0.664 AC: 190 AN: 286

European-Non Finnish (NFE) AF: 0.539 AC: 36302 AN: 67362

Other (OTH) AF: 0.528 AC: 1077 AN: 2040

Alfa AF: 0.533 Hom.: 11440

Bravo AF: 0.488

Asia WGS AF: 0.680 AC: 2364 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs2659915; hg19: chr7-66153101;