rs2478046

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/16 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286762.3. 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
	RUBCNL	NM_025113.5	MANE Select	c.*51C>T		3_prime_UTR	Exon 15 of 15	NP_079389.2	Q9H714-5
	RUBCNL	NM_001286762.3		c.1886C>T	p.Pro629Leu	missense	Exon 13 of 13	NP_001273691.1	Q9H714-4
	RUBCNL	NM_001286761.2		c.*51C>T		3_prime_UTR	Exon 15 of 15	NP_001273690.1	Q9H714-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUBCNL	ENST00000429979.6	TSL:5 MANE Select	c.*51C>T		3_prime_UTR	Exon 15 of 15	ENSP00000396935.1	Q9H714-5
	RUBCNL	ENST00000378784.8	TSL:1	c.*51C>T		3_prime_UTR	Exon 15 of 15	ENSP00000368061.4	Q9H714-3
	RUBCNL	ENST00000378797.6	TSL:1	c.*51C>T		3_prime_UTR	Exon 13 of 13	ENSP00000368074.3	A0A0A0MRV7

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

GnomAD2 exomes AF: 0.111 AC: 23820 AN: 214038 AF XY: 0.110

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 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

African (AFR) AF: 0.147 AC: 4853 AN: 33038

American (AMR) AF: 0.0840 AC: 3479 AN: 41396

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 2180 AN: 25540

East Asian (EAS) AF: 0.00221 AC: 86 AN: 38850

South Asian (SAS) AF: 0.0855 AC: 7106 AN: 83134

European-Finnish (FIN) AF: 0.120 AC: 6215 AN: 51966

Middle Eastern (MID) AF: 0.107 AC: 613 AN: 5736

European-Non Finnish (NFE) AF: 0.147 AC: 160658 AN: 1095560

Other (OTH) AF: 0.124 AC: 7384 AN: 59336

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

African (AFR) AF: 0.143 AC: 5942 AN: 41436

American (AMR) AF: 0.101 AC: 1548 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 316 AN: 3464

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5176

South Asian (SAS) AF: 0.0804 AC: 388 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1178 AN: 10558

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9762 AN: 67990

Other (OTH) AF: 0.123 AC: 258 AN: 2102

Alfa AF: 0.134 Hom.: 3757

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
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
PhyloP100		-0.17
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
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: rs2478046; hg19: chr13-46917469; COSMIC: COSV59788050;