dbSNP rs2478046: RUBCNL:c.*51C>T (chr13-46343334-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025113.5(RUBCNL):c.*51C>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 0.134 in 1,586,588 control chromosomes in the GnomAD database, including 15,149 homozygotes. In-silico tool predicts a benign outcome for this variant. 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_025113.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.169

Publications

18 publications found

Variant links:

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]

RUBCNL links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUBCNL	NM_025113.5 link	c.*51C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000429979.6	NP_079389.2	Q9H714-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUBCNL	ENST00000429979.6 link	c.*51C>T		3_prime_UTR_variant	Exon 15 of 15	5	NM_025113.5	ENSP00000396935.1		Q9H714-5

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19551

AN:

151914

Hom.:

1368

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.132

AC XY:

94167

AN XY:

711150

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

7484

14967

22451

29934

37418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5724

11448

17172

22896

28620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.129

AC:

19570

AN:

152032

Hom.:

1372

Cov.:

AF XY:

0.124

AC XY:

9182

AN XY:

74318

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9762

AN:

67990

Other (OTH)

AF:

0.123

AC:

258

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

873

1746

2618

3491

4364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.2

(source)

DANN

Benign

0.61

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.1

PhyloP100

-0.17

PROVEAN

Benign

1.4

REVEL

Benign

0.060

Sift

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.041

ClinPred

0.0067

GERP RS

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over