Genetic Variant NM_014633.5:c.2227-51G>A (chr11-10770436-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.368

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.2227-51G>A		intron_variant	Intron 17 of 24	ENST00000361367.7	NP_055448.1	Q6PD62
CTR9	NM_001346279.2 link	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 link	c.2227-51G>A		intron_variant	Intron 17 of 24	1	NM_014633.5	ENSP00000355013.2		Q6PD62

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41671

AN:

151990

Hom.:

9359

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.143

AC XY:

102451

AN XY:

716904

show subpopulations

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.:

AF XY:

0.271

AC XY:

20145

AN XY:

74374

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over