chr2-237590801-C-T

Position:

• chr2-237590801-C-T

Variant summary

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

The ENST00000392001.6(RAB17):​c.-338G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 156,594 control chromosomes in the GnomAD database, including 1,104 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 0.11 (1098 hom., cov: 32)
  • Exomes 𝑓: 0.035 (6 hom.)
• Consequence: RAB17 ENST00000392001.6 5_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

Genes affected

RAB17 (HGNC:16523): (RAB17, member RAS oncogene family) The Rab subfamily of small GTPases plays an important role in the regulation of membrane trafficking. RAB17 is an epithelial cell-specific GTPase (Lutcke et al., 1993 [PubMed 8486736]).[supplied by OMIM, Oct 2009]

RAB17-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB17-DT	XR_001739965.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB17	ENST00000392001.6	c.-338G>A		5_prime_UTR_variant, NMD_transcript_variant	1/5	1		ENSP00000375858
RAB17	ENST00000487008.1	n.282G>A		non_coding_transcript_exon_variant	2/2	3
RAB17	ENST00000409822.1			upstream_gene_variant		5		ENSP00000386589

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17161 AN: 152008 Hom.: 1100 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0349 AC: 156 AN: 4468 Hom.: 6 Cov.: 0 AF XY: 0.0355 AC XY: 84 AN XY: 2368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00746

Gnomad4 ASJ exome AF: 0.00877

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0318

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0402

Gnomad4 OTH exome AF: 0.0313

GnomAD4 genome AF: 0.113 AC: 17159 AN: 152126 Hom.: 1098 Cov.: 32 AF XY: 0.111 AC XY: 8222 AN XY: 74378

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0885

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.105

Alfa AF: 0.125 Hom.: 1381

Bravo AF: 0.106

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.2
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292873; hg19: chr2-238499444;