rs252108

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000511961.5(RNF14):c.-7+781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,228 control chromosomes in the GnomAD database, including 50,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.81 ( 50180 hom., cov: 31)

Exomes 𝑓: 0.85 ( 45 hom. )

Consequence

RNF14
ENST00000511961.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

Publications

3 publications found

Variant links:

Genes affected

RNF14 (HGNC:10058): (ring finger protein 14) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein interacts with androgen receptor (AR) and may function as a coactivator that induces AR target gene expression in prostate. A dominant negative mutant of this gene has been demonstrated to inhibit the AR-mediated growth of prostate cancer. This protein also interacts with class III ubiquitin-conjugating enzymes (E2s) and may act as a ubiquitin-ligase (E3) in the ubiquitination of certain nuclear proteins. Six alternatively spliced transcript variants encoding two distinct isoforms have been reported. [provided by RefSeq, Jan 2011]

RNF14 links:

PCDH12 (HGNC:8657): (protocadherin 12) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

PCDH12 Gene-Disease associations (from GenCC):

diencephalic-mesencephalic junction dysplasia syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
diencephalic-mesencephalic junction dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PCDH12 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000511961.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-141959206-A-G is Benign according to our data. Variant chr5-141959206-A-G is described in ClinVar as Benign. ClinVar VariationId is 1294900.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511961.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNF14	ENST00000511961.5	TSL:3	c.-7+781A>G	intron	N/A	ENSP00000423420.1	D6RA38
RNF14	ENST00000506822.5	TSL:5	c.-181+781A>G	intron	N/A	ENSP00000423273.1	D6R996
PCDH12	ENST00000512221.2	TSL:3	n.259-961T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.811

AC:

123213

AN:

151984

Hom.:

50155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.831

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.816

GnomAD4 exome

AF:

0.849

AC:

107

AN:

126

Hom.:

AF XY:

0.838

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.800

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.851

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.811

AC:

123297

AN:

152102

Hom.:

50180

Cov.:

AF XY:

0.813

AC XY:

60432

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.796

AC:

33026

AN:

41494

American (AMR)

AF:

0.875

AC:

13385

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.843

AC:

2924

AN:

3468

East Asian (EAS)

AF:

0.993

AC:

5136

AN:

5174

South Asian (SAS)

AF:

0.872

AC:

4205

AN:

4820

European-Finnish (FIN)

AF:

0.737

AC:

7784

AN:

10560

Middle Eastern (MID)

AF:

0.825

AC:

241

AN:

292

European-Non Finnish (NFE)

AF:

0.798

AC:

54270

AN:

67982

Other (OTH)

AF:

0.813

AC:

1716

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1222

2444

3667

4889

6111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.809

Hom.:

54234

Bravo

AF:

0.824

Asia WGS

AF:

0.895

AC:

3115

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.31

(source)

DANN

Benign

0.56

PhyloP100

-1.7

PromoterAI

0.0099

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over