5-141959206-A-G

Variant names:

• chr5-141959206-A-G
• rs252108
• ENST00000511961.5:c.-7+781A>G

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+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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74
• Publications: 3 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), G2P, Ambry Genetics
• 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=-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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 31

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.: 45 AF XY: 0.838 AC XY: 62 AN XY: 74

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.800 AC: 24 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.851 AC: 63 AN: 74

Other (OTH) AF: 1.00 AC: 12 AN: 12

GnomAD4 genome AF: 0.811 AC: 123297 AN: 152102 Hom.: 50180 Cov.: 31 AF XY: 0.813 AC XY: 60432 AN XY: 74340

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

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

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-1.7
PromoterAI		0.0099	Neutral

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.

Other links and lift over

dbSNP: rs252108;

hg19: chr5-141338771;