Variant chr17-78892237-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001243540.2(CEP295NL):c.267C>T(p.Gly89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,550,974 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 55 hom. )

Consequence

CEP295NL
NM_001243540.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.34

Variant links:

Genes affected

CEP295NL (HGNC:44659): (CEP295 N-terminal like) Predicted to enable microtubule binding activity. Predicted to be involved in regulation of centriole replication. Predicted to be located in motile cilium. Predicted to be active in centriole; centrosome; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CEP295NL links:

TIMP2 (HGNC:11821): (TIMP metallopeptidase inhibitor 2) This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

TIMP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-78892237-G-A is Benign according to our data. Variant chr17-78892237-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648382.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP295NL	NM_001243540.2 linkuse as main transcript	c.267C>T	p.Gly89=	synonymous_variant	3/3	ENST00000322630.3
TIMP2	NM_003255.5 linkuse as main transcript	c.131-18318C>T		intron_variant		ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP295NL	ENST00000322630.3 linkuse as main transcript	c.267C>T	p.Gly89=	synonymous_variant	3/3	2	NM_001243540.2	P1
TIMP2	ENST00000262768.11 linkuse as main transcript	c.131-18318C>T		intron_variant		1	NM_003255.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00572

AC:

870

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0206

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00804

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00572

AC:

859

AN:

150226

Hom.:

AF XY:

0.00549

AC XY:

443

AN XY:

80702

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.000854

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00257

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.00790

Gnomad OTH exome

AF:

0.00412

GnomAD4 exome

AF:

0.00785

AC:

10979

AN:

1398640

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

5240

AN XY:

689830

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.000896

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00875

Gnomad4 OTH exome

AF:

0.00597

GnomAD4 genome

AF:

0.00571

AC:

870

AN:

152334

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

466

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0206

Gnomad4 NFE

AF:

0.00804

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.00388

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

CEP295NL: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.14

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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