rs4789860

Variant names:

• chr17-78902551-T-C
• rs4789860
• NM_001243540.2:c.-99+583A>G

Variant summary

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

The NM_001243540.2(CEP295NL):​c.-99+583A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,236 control chromosomes in the GnomAD database, including 13,163 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 0.41 (13145 hom., cov: 32)
  • Exomes 𝑓: 0.40 (18 hom.)
• Consequence: CEP295NL NM_001243540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 7 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 = 0.441 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP295NL	NM_001243540.2	MANE Select	c.-99+583A>G		intron	N/A	NP_001230469.1	Q96MC4
	TIMP2	NM_003255.5	MANE Select	c.130+22408A>G		intron	N/A	NP_003246.1	P16035
	CEP295NL	NM_001243541.2		c.-334+583A>G		intron	N/A	NP_001230470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP295NL	ENST00000322630.3	TSL:2 MANE Select	c.-99+583A>G		intron	N/A	ENSP00000312767.2	Q96MC4
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.130+22408A>G		intron	N/A	ENSP00000262768.6	P16035
	CEP295NL	ENST00000590267.6	TSL:2	c.-334+583A>G		intron	N/A	ENSP00000516640.1	A0A9L9PY45

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62817 AN: 151932 Hom.: 13148 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.398 AC: 74 AN: 186 Hom.: 18 AF XY: 0.390 AC XY: 53 AN XY: 136

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.400 AC: 64 AN: 160

Other (OTH) AF: 0.600 AC: 6 AN: 10

GnomAD4 genome AF: 0.413 AC: 62838 AN: 152050 Hom.: 13145 Cov.: 32 AF XY: 0.414 AC XY: 30803 AN XY: 74316

African (AFR) AF: 0.446 AC: 18522 AN: 41498

American (AMR) AF: 0.388 AC: 5918 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1528 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5166

South Asian (SAS) AF: 0.341 AC: 1644 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 5007 AN: 10582

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27768 AN: 67932

Other (OTH) AF: 0.419 AC: 885 AN: 2110

Alfa AF: 0.416 Hom.: 5084

Bravo AF: 0.408

Asia WGS AF: 0.260 AC: 904 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	4.4
DANN	Benign	0.23
PhyloP100		-0.28
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: rs4789860; hg19: chr17-76898633;