17-78902983-C-A

Position:

• chr17-78902983-C-A

Variant summary

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

The NM_001243540.2(CEP295NL):​c.-99+151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,090 control chromosomes in the GnomAD database, including 20,937 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 0.51 (20937 hom., cov: 33)
• Consequence: CEP295NL NM_001243540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295NL	NM_001243540.2	c.-99+151G>T		intron_variant		ENST00000322630.3	NP_001230469.1
TIMP2	NM_003255.5	c.130+21976G>T		intron_variant		ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11	c.130+21976G>T		intron_variant		1	NM_003255.5	ENSP00000262768	P1
CEP295NL	ENST00000322630.3	c.-99+151G>T		intron_variant		2	NM_001243540.2	ENSP00000312767	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78164 AN: 151972 Hom.: 20925 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.514 AC: 78210 AN: 152090 Hom.: 20937 Cov.: 33 AF XY: 0.511 AC XY: 38022 AN XY: 74358

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.527

Alfa AF: 0.455 Hom.: 2346

Bravo AF: 0.516

Asia WGS AF: 0.649 AC: 2257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.54

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: rs7211674; hg19: chr17-76899065;