rs2132517

Variant names:

• chr11-10770436-G-A
• rs2132517
• NM_014633.5:c.2227-51G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-10770436-G-A
• chr11-10770436-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014633.5(CTR9):​c.2227-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,594,652 control chromosomes in the GnomAD database, including 29,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (9379 hom., cov: 33)
  • Exomes 𝑓: 0.14 (20572 hom.)
• Consequence: CTR9 NM_014633.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368
• Publications: 8 publications found

Genes affected

CTR9 (HGNC:16850): (CTR9 homolog, Paf1/RNA polymerase II complex component) The protein encoded by this gene is a component of the PAF1 complex, which associates with RNA polymerase II and functions in transcriptional regulation and elongation. This complex also plays a role in the modification of histones. [provided by RefSeq, Oct 2016]

CTR9 Gene-Disease associations (from GenCC):

• childhood kidney Wilms tumor

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• CTR9-related neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-10770436-G-A is Benign according to our data. Variant chr11-10770436-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTR9	NM_014633.5	c.2227-51G>A		intron_variant	Intron 17 of 24	ENST00000361367.7	NP_055448.1
CTR9	NM_001346279.2	c.2227-51G>A		intron_variant	Intron 17 of 23		NP_001333208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTR9	ENST00000361367.7	c.2227-51G>A		intron_variant	Intron 17 of 24	1	NM_014633.5	ENSP00000355013.2
CTR9	ENST00000715696.1	c.2227-51G>A		intron_variant	Intron 17 of 24			ENSP00000520504.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41671 AN: 151990 Hom.: 9359 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.188 AC: 45161 AN: 240396 AF XY: 0.175

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.0711

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.144 AC: 208394 AN: 1442544 Hom.: 20572 Cov.: 29 AF XY: 0.143 AC XY: 102451 AN XY: 716904

African (AFR) AF: 0.633 AC: 20547 AN: 32446

American (AMR) AF: 0.289 AC: 12134 AN: 41938

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3707 AN: 25436

East Asian (EAS) AF: 0.222 AC: 8770 AN: 39474

South Asian (SAS) AF: 0.165 AC: 13831 AN: 83836

European-Finnish (FIN) AF: 0.0710 AC: 3771 AN: 53106

Middle Eastern (MID) AF: 0.111 AC: 629 AN: 5678

European-Non Finnish (NFE) AF: 0.123 AC: 135260 AN: 1101120

Other (OTH) AF: 0.164 AC: 9745 AN: 59510

GnomAD4 genome AF: 0.274 AC: 41742 AN: 152108 Hom.: 9379 Cov.: 33 AF XY: 0.271 AC XY: 20145 AN XY: 74374

African (AFR) AF: 0.617 AC: 25591 AN: 41470

American (AMR) AF: 0.267 AC: 4082 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1167 AN: 5170

South Asian (SAS) AF: 0.166 AC: 799 AN: 4826

European-Finnish (FIN) AF: 0.0746 AC: 790 AN: 10592

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8097 AN: 67996

Other (OTH) AF: 0.247 AC: 520 AN: 2108

Alfa AF: 0.180 Hom.: 13455

Bravo AF: 0.305

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.60
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2132517; hg19: chr11-10791983; COSMIC: COSV63728126; COSMIC: COSV63728126;