chr17-78901393-A-G

Position:

• chr17-78901393-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.88).
• 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
CEP295NL	NM_001243540.2	c.44+392T>C		intron_variant		ENST00000322630.3
TIMP2	NM_003255.5	c.130+23566T>C		intron_variant		ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMP2	ENST00000262768.11	c.130+23566T>C		intron_variant		1	NM_003255.5	P1
CEP295NL	ENST00000322630.3	c.44+392T>C		intron_variant		2	NM_001243540.2	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74488 AN: 151868 Hom.: 19191 Cov.: 31

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

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

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

Other links and lift over

dbSNP: rs2889529; hg19: chr17-76897475;