17-78901393-A-G

Variant names:

• chr17-78901393-A-G
• rs2889529
• NM_001243540.2:c.44+392T>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.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
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 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.44+392T>C		intron	N/A	NP_001230469.1
	TIMP2	NM_003255.5	MANE Select	c.130+23566T>C		intron	N/A	NP_003246.1
	CEP295NL	NM_001243541.2		c.-192+392T>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.44+392T>C		intron	N/A	ENSP00000312767.2
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.130+23566T>C		intron	N/A	ENSP00000262768.6
	CEP295NL	ENST00000590267.6	TSL:2	c.-192+392T>C		intron	N/A	ENSP00000516640.1

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

African (AFR) AF: 0.634 AC: 1615 AN: 2546

American (AMR) AF: 0.393 AC: 1941 AN: 4942

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1053 AN: 2406

East Asian (EAS) AF: 0.241 AC: 1035 AN: 4292

South Asian (SAS) AF: 0.379 AC: 4668 AN: 12302

European-Finnish (FIN) AF: 0.461 AC: 1735 AN: 3766

Middle Eastern (MID) AF: 0.563 AC: 198 AN: 352

European-Non Finnish (NFE) AF: 0.414 AC: 21679 AN: 52400

Other (OTH) AF: 0.419 AC: 2060 AN: 4916

GnomAD4 genome AF: 0.490 AC: 74547 AN: 151986 Hom.: 19210 Cov.: 31 AF XY: 0.493 AC XY: 36608 AN XY: 74288

African (AFR) AF: 0.653 AC: 27080 AN: 41460

American (AMR) AF: 0.421 AC: 6415 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1576 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5166

South Asian (SAS) AF: 0.401 AC: 1932 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5513 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29152 AN: 67968

Other (OTH) AF: 0.477 AC: 1007 AN: 2110

Alfa AF: 0.445 Hom.: 54880

Bravo AF: 0.490

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.34
PhyloP100		0.53
PromoterAI		0.011	Neutral
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: rs2889529; hg19: chr17-76897475;