chr17-78894782-A-G

Variant names:

• chr17-78894782-A-G
• rs2376999
• NM_001243540.2:c.45-2323T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243540.2(CEP295NL):​c.45-2323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,004 control chromosomes in the GnomAD database, including 9,578 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 (9578 hom., cov: 32)
• Consequence: CEP295NL NM_001243540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243540.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP295NL	NM_001243540.2	MANE Select	c.45-2323T>C		intron	N/A	NP_001230469.1
	TIMP2	NM_003255.5	MANE Select	c.131-20863T>C		intron	N/A	NP_003246.1
	CEP295NL	NM_001243541.2		c.-191-2262T>C		intron	N/A	NP_001230470.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP295NL	ENST00000322630.3	TSL:2 MANE Select	c.45-2323T>C		intron	N/A	ENSP00000312767.2
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.131-20863T>C		intron	N/A	ENSP00000262768.6
	CEP295NL	ENST00000590267.6	TSL:2	c.-191-2262T>C		intron	N/A	ENSP00000516640.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41373 AN: 151888 Hom.: 9546 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.273 AC: 41457 AN: 152004 Hom.: 9578 Cov.: 32 AF XY: 0.271 AC XY: 20132 AN XY: 74314

African (AFR) AF: 0.635 AC: 26275 AN: 41370

American (AMR) AF: 0.157 AC: 2402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5174

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4818

European-Finnish (FIN) AF: 0.125 AC: 1319 AN: 10572

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7793 AN: 68004

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.142 Hom.: 6140

Bravo AF: 0.290

Asia WGS AF: 0.298 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.35
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2376999; hg19: chr17-76890864;