11-10752577-G-A

Position:

• chr11-10752577-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014633.5(CTR9):​c.46-95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 818,222 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (31 hom.)
• Consequence: CTR9 NM_014633.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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=-0.88).
• BP6: Variant 11-10752577-G-A is Benign according to our data. Variant chr11-10752577-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00606 (923/152258) while in subpopulation NFE AF= 0.0101 (689/68020). AF 95% confidence interval is 0.0095. There are 3 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 923 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTR9	NM_014633.5	c.46-95G>A		intron_variant		ENST00000361367.7
CTR9	NM_001346279.2	c.46-95G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTR9	ENST00000361367.7	c.46-95G>A		intron_variant		1	NM_014633.5	P1
CTR9	ENST00000524523.1	c.7-95G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00607 AC: 923 AN: 152140 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00734 AC: 4887 AN: 665964 Hom.: 31 AF XY: 0.00692 AC XY: 2469 AN XY: 356622

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.000572

Gnomad4 ASJ exome AF: 0.000265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0179

Gnomad4 NFE exome AF: 0.00939

Gnomad4 OTH exome AF: 0.00542

GnomAD4 genome AF: 0.00606 AC: 923 AN: 152258 Hom.: 3 Cov.: 32 AF XY: 0.00633 AC XY: 471 AN XY: 74460

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00995 Hom.: 1

Bravo AF: 0.00460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.78

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: rs192886164; hg19: chr11-10774124;