rs2132517

chr11-10770436-G-Achr11-10770436-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.368

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1234240.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
CTR9	NM_014633.5	c.2227-51G>A		intron_variant		ENST00000361367.7
CTR9	NM_001346279.2	c.2227-51G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTR9	ENST00000361367.7	c.2227-51G>A		intron_variant		1	NM_014633.5	P1

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

GnomAD3 exomes AF: 0.188 AC: 45161 AN: 240396 Hom.: 6492 AF XY: 0.175 AC XY: 22774 AN XY: 130168

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 SAS exome AF: 0.167

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

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.164

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

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.247

Alfa AF: 0.149 Hom.: 4930

Bravo AF: 0.305

Asia WGS AF: 0.233 AC: 810 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

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.6
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs2132517; hg19: chr11-10791983; COSMIC: COSV63728126; COSMIC: COSV63728126;