rs11744911

Variant names:

• chr5-141959001-C-G
• rs11744911
• ENST00000511961.5:c.-7+576C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 139 AR gene

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+576C>G		intron	N/A	ENSP00000423420.1	D6RA38
	RNF14	ENST00000506822.5	TSL:5	c.-181+576C>G		intron	N/A	ENSP00000423273.1	D6R996
	PCDH12	ENST00000512221.2	TSL:3	n.259-756G>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.0556 AC: 1 AN: 18

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0698 AC: 6 AN: 86

Other (OTH) AF: 0.125 AC: 1 AN: 8

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

African (AFR) AF: 0.0107 AC: 444 AN: 41568

American (AMR) AF: 0.0274 AC: 419 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5178

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4820

European-Finnish (FIN) AF: 0.0578 AC: 614 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3343 AN: 68004

Other (OTH) AF: 0.0412 AC: 87 AN: 2110

Alfa AF: 0.0394 Hom.: 12

Bravo AF: 0.0313

Asia WGS AF: 0.0190 AC: 66 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	-0.78
CADD	Benign	9.8
DANN	Benign	0.76
PhyloP100		0.088
PromoterAI		0.059	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs11744911; hg19: chr5-141338566;