5-141959262-G-A

Position:

• chr5-141959262-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF14	XM_047417903.1	c.-181+837G>A		intron_variant			XP_047273859.1
RNF14	XM_047417904.1	c.-181+9852G>A		intron_variant			XP_047273860.1
RNF14	XM_047417908.1	c.-181+9852G>A		intron_variant			XP_047273864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF14	ENST00000511961.5	c.-7+837G>A		intron_variant		3		ENSP00000423420.1
RNF14	ENST00000506822.5	c.-181+837G>A		intron_variant		5		ENSP00000423273.1
PCDH12	ENST00000512221.2	n.259-1017C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0942

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.106 Hom.: 306

Bravo AF: 0.0864

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

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