chr9-17487947-T-G

Variant names:

• chr9-17487947-T-G
• rs2383024
• NM_017738.4:c.4119+881T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017738.4(CNTLN):​c.4119+881T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,076 control chromosomes in the GnomAD database, including 7,859 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 0.30 (7859 hom., cov: 32)
• Consequence: CNTLN NM_017738.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTLN	NM_017738.4	c.4119+881T>G		intron_variant	Intron 25 of 25	ENST00000380647.8	NP_060208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTLN	ENST00000380647.8	c.4119+881T>G		intron_variant	Intron 25 of 25	1	NM_017738.4	ENSP00000370021.3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46176 AN: 151958 Hom.: 7850 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.304 AC: 46200 AN: 152076 Hom.: 7859 Cov.: 32 AF XY: 0.304 AC XY: 22564 AN XY: 74332

African (AFR) AF: 0.156 AC: 6494 AN: 41522

American (AMR) AF: 0.411 AC: 6270 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2195 AN: 5164

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4822

European-Finnish (FIN) AF: 0.346 AC: 3662 AN: 10580

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23869 AN: 67958

Other (OTH) AF: 0.321 AC: 675 AN: 2100

Alfa AF: 0.307 Hom.: 7035

Bravo AF: 0.310

Asia WGS AF: 0.319 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		1.2
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: rs2383024; hg19: chr9-17487945; COSMIC: COSV52082913;