14-64946055-G-A

Position:

• chr14-64946055-G-A

Variant summary

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

The NM_001308154.2(RAB15):​c.*2299C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 152,632 control chromosomes in the GnomAD database, including 344 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 0.061 (344 hom., cov: 32)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: RAB15 NM_001308154.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

RAB15 (HGNC:20150): (RAB15, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Involved in positive regulation of regulated secretory pathway. Located in cilium; endosome membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CHURC1-FNTB (HGNC:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

RAB15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB15	NM_001308154.2	c.*2299C>T		3_prime_UTR_variant	7/7	ENST00000533601.7	NP_001295083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB15	ENST00000533601	c.*2299C>T		3_prime_UTR_variant	7/7	1	NM_001308154.2	ENSP00000434103.3
CHURC1-FNTB	ENST00000549987.1	c.246+19975G>A		intron_variant		2		ENSP00000447121.2

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9266 AN: 152054 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0751

GnomAD4 exome AF: 0.0370 AC: 17 AN: 460 Hom.: 0 Cov.: 0 AF XY: 0.0321 AC XY: 9 AN XY: 280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0350

Gnomad4 NFE exome AF: 0.0769

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0609 AC: 9263 AN: 152172 Hom.: 344 Cov.: 32 AF XY: 0.0586 AC XY: 4358 AN XY: 74382

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.0274

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0612 Hom.: 168

Bravo AF: 0.0641

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.53

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: rs10121; hg19: chr14-65412773; COSMIC: COSV50824794; COSMIC: COSV50824794;