ENST00000511961.5:c.-7+837G>A

Variant names:

• chr5-141959262-G-A
• rs3761762
• ENST00000511961.5:c.-7+837G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000511961.5(RNF14):​c.-7+837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 151,976 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.091 (757 hom., cov: 33)
• Consequence: RNF14 ENST00000511961.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 5 publications found

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]

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), Ambry Genetics, G2P
• diencephalic-mesencephalic junction dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 5-141959262-G-A is Benign according to our data. Variant chr5-141959262-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF14	ENST00000511961.5	TSL:3	c.-7+837G>A		intron	N/A	ENSP00000423420.1	D6RA38
	RNF14	ENST00000506822.5	TSL:5	c.-181+837G>A		intron	N/A	ENSP00000423273.1	D6R996
	PCDH12	ENST00000512221.2	TSL:3	n.259-1017C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13861 AN: 151858 Hom.: 757 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0912 AC: 13866 AN: 151976 Hom.: 757 Cov.: 33 AF XY: 0.0923 AC XY: 6857 AN XY: 74268

African (AFR) AF: 0.0500 AC: 2069 AN: 41400

American (AMR) AF: 0.0761 AC: 1163 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3468

East Asian (EAS) AF: 0.00946 AC: 49 AN: 5180

South Asian (SAS) AF: 0.0942 AC: 454 AN: 4818

European-Finnish (FIN) AF: 0.116 AC: 1222 AN: 10520

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8203 AN: 67996

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.101 Hom.: 426

Bravo AF: 0.0864

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.24
PhyloP100		-1.3
PromoterAI		-0.00030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3761762; hg19: chr5-141338827; COSMIC: COSV51520287;