rs10121

Variant names:

• chr14-64946055-G-A
• rs10121
• NM_001308154.2:c.*2299C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-64946055-G-A
• chr14-64946055-G-C
• chr14-64946055-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308154.2. 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
	RAB15	NM_001308154.2	MANE Select	c.*2299C>T		3_prime_UTR	Exon 7 of 7	NP_001295083.1	G5EMR8
	RAB15	NM_198686.3		c.*2442C>T		3_prime_UTR	Exon 7 of 7	NP_941959.1	P59190-2
	RAB15	NM_001330182.2		c.*2299C>T		3_prime_UTR	Exon 8 of 8	NP_001317111.1	G3V562

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB15	ENST00000533601.7	TSL:1 MANE Select	c.*2299C>T		3_prime_UTR	Exon 7 of 7	ENSP00000434103.3	P59190-1
	RAB15	ENST00000267512.9	TSL:1	c.*2442C>T		3_prime_UTR	Exon 7 of 7	ENSP00000267512.5	P59190-2
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+19975G>A		intron	N/A	ENSP00000447121.2	B4DL54

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0350 AC: 15 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0769 AC: 2 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0367 AC: 1522 AN: 41506

American (AMR) AF: 0.0679 AC: 1039 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.0773 AC: 400 AN: 5172

South Asian (SAS) AF: 0.0442 AC: 213 AN: 4818

European-Finnish (FIN) AF: 0.0274 AC: 290 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5128 AN: 67994

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0680 Hom.: 735

Bravo AF: 0.0641

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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