5-141959001-C-G

Position:

• chr5-141959001-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000511961.5(RNF14):​c.-7+576C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,406 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (139 hom., cov: 33)
  • Exomes 𝑓: 0.073 (0 hom.)
• Consequence: RNF14 ENST00000511961.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-141959001-C-G is Benign according to our data. Variant chr5-141959001-C-G is described in ClinVar as [Benign]. Clinvar id is 1263863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0349 (5317/152282) while in subpopulation NFE AF= 0.0492 (3343/68004). AF 95% confidence interval is 0.0478. There are 139 homozygotes in gnomad4. There are 2618 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 139 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF14	XM_047417903.1	c.-181+576C>G		intron_variant			XP_047273859.1
RNF14	XM_047417904.1	c.-181+9591C>G		intron_variant			XP_047273860.1
RNF14	XM_047417908.1	c.-181+9591C>G		intron_variant			XP_047273864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF14	ENST00000506822.5	c.-181+576C>G		intron_variant		5		ENSP00000423273
RNF14	ENST00000511961.5	c.-7+576C>G		intron_variant		3		ENSP00000423420
PCDH12	ENST00000512221.2	n.259-756G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5310 AN: 152164 Hom.: 139 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0417

GnomAD4 exome AF: 0.0726 AC: 9 AN: 124 Hom.: 0 Cov.: 0 AF XY: 0.0532 AC XY: 5 AN XY: 94

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0698

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0349 AC: 5317 AN: 152282 Hom.: 139 Cov.: 33 AF XY: 0.0352 AC XY: 2618 AN XY: 74466

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0394 Hom.: 12

Bravo AF: 0.0313

Asia WGS AF: 0.0190 AC: 66 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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.8
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11744911; hg19: chr5-141338566;