chr17-78901393-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001243540.2(CEP295NL):​c.44+392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 239,908 control chromosomes in the GnomAD database, including 27,257 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 0.49 ( 19210 hom., cov: 31)
Exomes 𝑓: 0.41 ( 8047 hom. )

Consequence

CEP295NL
NM_001243540.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.531
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CEP295NLNM_001243540.2 linkuse as main transcriptc.44+392T>C intron_variant ENST00000322630.3
TIMP2NM_003255.5 linkuse as main transcriptc.130+23566T>C intron_variant ENST00000262768.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TIMP2ENST00000262768.11 linkuse as main transcriptc.130+23566T>C intron_variant 1 NM_003255.5 P1
CEP295NLENST00000322630.3 linkuse as main transcriptc.44+392T>C intron_variant 2 NM_001243540.2 P1

Frequencies

GnomAD3 genomes
AF:
0.490
AC:
74488
AN:
151868
Hom.:
19191
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.653
Gnomad AMI
AF:
0.373
Gnomad AMR
AF:
0.421
Gnomad ASJ
AF:
0.455
Gnomad EAS
AF:
0.270
Gnomad SAS
AF:
0.401
Gnomad FIN
AF:
0.523
Gnomad MID
AF:
0.497
Gnomad NFE
AF:
0.429
Gnomad OTH
AF:
0.477
GnomAD4 exome
AF:
0.409
AC:
35984
AN:
87922
Hom.:
8047
AF XY:
0.406
AC XY:
18948
AN XY:
46720
show subpopulations
Gnomad4 AFR exome
AF:
0.634
Gnomad4 AMR exome
AF:
0.393
Gnomad4 ASJ exome
AF:
0.438
Gnomad4 EAS exome
AF:
0.241
Gnomad4 SAS exome
AF:
0.379
Gnomad4 FIN exome
AF:
0.461
Gnomad4 NFE exome
AF:
0.414
Gnomad4 OTH exome
AF:
0.419
GnomAD4 genome
AF:
0.490
AC:
74547
AN:
151986
Hom.:
19210
Cov.:
31
AF XY:
0.493
AC XY:
36608
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.653
Gnomad4 AMR
AF:
0.421
Gnomad4 ASJ
AF:
0.455
Gnomad4 EAS
AF:
0.269
Gnomad4 SAS
AF:
0.401
Gnomad4 FIN
AF:
0.523
Gnomad4 NFE
AF:
0.429
Gnomad4 OTH
AF:
0.477
Alfa
AF:
0.439
Hom.:
22039
Bravo
AF:
0.490
Asia WGS
AF:
0.339
AC:
1181
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
4.3
DANN
Benign
0.34

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2889529; hg19: chr17-76897475; API