rs3744787

Positions:

• chr17-78897589-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+4196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,138 control chromosomes in the GnomAD database, including 9,125 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 0.27 (9122 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3 hom.)
• Consequence: CEP295NL NM_001243540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

ENSG00000279339 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295NL	NM_001243540.2	c.44+4196T>C		intron_variant		ENST00000322630.3	NP_001230469.1
TIMP2	NM_003255.5	c.131-23670T>C		intron_variant		ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP295NL	ENST00000322630.3	c.44+4196T>C		intron_variant		2	NM_001243540.2	ENSP00000312767.2
TIMP2	ENST00000262768.11	c.131-23670T>C		intron_variant		1	NM_003255.5	ENSP00000262768.6

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41059 AN: 151954 Hom.: 9093 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.188 AC: 12 AN: 64 Hom.: 3 Cov.: 0 AF XY: 0.190 AC XY: 8 AN XY: 42

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.271 AC: 41144 AN: 152074 Hom.: 9122 Cov.: 32 AF XY: 0.263 AC XY: 19551 AN XY: 74344

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0874

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.242

Alfa AF: 0.160 Hom.: 3653

Bravo AF: 0.289

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.76
DANN	Benign	0.28

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: rs3744787; hg19: chr17-76893671;