rs2478046

Variant names:

• chr13-46343334-G-A
• rs2478046
• NM_025113.5:c.*51C>T

Variant summary

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

The NM_001286762.3(RUBCNL):​c.1886C>T​(p.Pro629Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,586,588 control chromosomes in the GnomAD database, including 15,149 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1372 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13777 hom.)
• Consequence: RUBCNL NM_001286762.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

RUBCNL (HGNC:20420): (rubicon like autophagy enhancer) This gene encodes a cysteine-rich protein that contains a putative zinc-RING and/or ribbon domain. The encoded protein is related to Run domain Beclin-1-interacting and cysteine-rich domain-containing protein, which plays a role in endocytic trafficking and autophagy. In cervical cancer cell lines, this gene is expressed at low levels and may function as a tumor suppressor. Promoter hypermethylation of this gene is observed in cervical cancer cell lines and tissue derived from human patients. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012407601).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUBCNL	NM_025113.5	c.*51C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000429979.6	NP_079389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUBCNL	ENST00000429979	c.*51C>T		3_prime_UTR_variant	Exon 15 of 15	5	NM_025113.5	ENSP00000396935.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19551 AN: 151914 Hom.: 1368 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0912

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.111 AC: 23820 AN: 214038 Hom.: 1499 AF XY: 0.110 AC XY: 12633 AN XY: 114724

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.0807

Gnomad ASJ exome AF: 0.0848

Gnomad EAS exome AF: 0.00450

Gnomad SAS exome AF: 0.0845

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.134 AC: 192574 AN: 1434556 Hom.: 13777 Cov.: 31 AF XY: 0.132 AC XY: 94167 AN XY: 711150

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0840

Gnomad4 ASJ exome AF: 0.0854

Gnomad4 EAS exome AF: 0.00221

Gnomad4 SAS exome AF: 0.0855

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.129 AC: 19570 AN: 152032 Hom.: 1372 Cov.: 32 AF XY: 0.124 AC XY: 9182 AN XY: 74318

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0912

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.123

Alfa AF: 0.136 Hom.: 2657

Bravo AF: 0.128

TwinsUK AF: 0.147 AC: 545

ALSPAC AF: 0.142 AC: 548

ESP6500AA AF: 0.140 AC: 371

ESP6500EA AF: 0.134 AC: 617

ExAC AF: 0.107 AC: 12881

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.2
DANN	Benign	0.61
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.041
ClinPred		0.0067	T
GERP RS		-0.87

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: rs2478046; hg19: chr13-46917469; COSMIC: COSV59788050;