9-17161529-G-T

Variant names:

• chr9-17161529-G-T
• rs10511633
• NM_017738.4:c.449+18153G>T

Variant summary

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

The NM_017738.4(CNTLN):​c.449+18153G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,096 control chromosomes in the GnomAD database, including 2,600 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 0.18 (2600 hom., cov: 32)
• Consequence: CNTLN NM_017738.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTLN	NM_017738.4	c.449+18153G>T		intron_variant	Intron 2 of 25	ENST00000380647.8	NP_060208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTLN	ENST00000380647.8	c.449+18153G>T		intron_variant	Intron 2 of 25	1	NM_017738.4	ENSP00000370021.3
CNTLN	ENST00000380641.4	c.449+18153G>T		intron_variant	Intron 2 of 6	2		ENSP00000370015.3
CNTLN	ENST00000484374.1	n.534-5289G>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27686 AN: 151976 Hom.: 2599 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.182 AC: 27690 AN: 152096 Hom.: 2600 Cov.: 32 AF XY: 0.183 AC XY: 13619 AN XY: 74372

African (AFR) AF: 0.216 AC: 8975 AN: 41506

American (AMR) AF: 0.199 AC: 3034 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3470

East Asian (EAS) AF: 0.191 AC: 990 AN: 5178

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4814

European-Finnish (FIN) AF: 0.148 AC: 1561 AN: 10564

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10582 AN: 67972

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.156 Hom.: 2160

Bravo AF: 0.188

Asia WGS AF: 0.237 AC: 820 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.66
PhyloP100		0.057
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: rs10511633; hg19: chr9-17161527;