9-17458874-C-T

Position:

• chr9-17458874-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017738.4(CNTLN):​c.3306+1159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,538 control chromosomes in the GnomAD database, including 43,381 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (43381 hom., cov: 31)
• Consequence: CNTLN NM_017738.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

Genes affected

CNTLN (HGNC:23432): (centlein) Enables protein domain specific binding activity; protein kinase binding activity; and protein-macromolecule adaptor activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in cytosol; microtubule organizing center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTLN	NM_017738.4	c.3306+1159C>T		intron_variant		ENST00000380647.8	NP_060208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTLN	ENST00000380647.8	c.3306+1159C>T		intron_variant		1	NM_017738.4	ENSP00000370021.3
CNTLN	ENST00000461247.1	n.443+1246C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112776 AN: 151420 Hom.: 43378 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.744 AC: 112809 AN: 151538 Hom.: 43381 Cov.: 31 AF XY: 0.748 AC XY: 55422 AN XY: 74074

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.765

Alfa AF: 0.756 Hom.: 6886

Bravo AF: 0.734

Asia WGS AF: 0.749 AC: 2596 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.030
DANN	Benign	0.58

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: rs10810790; hg19: chr9-17458872;