rs4796813

Variant names:

• chr17-78879182-A-G
• rs4796813
• NM_003255.5:c.131-5263T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-78879182-A-G
• chr17-78879182-A-T

Variant summary

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

The NM_003255.5(TIMP2):​c.131-5263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,304 control chromosomes in the GnomAD database, including 66,900 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 0.94 (66900 hom., cov: 33)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• Publications: 7 publications found

Genes affected

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003255.5. 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
	TIMP2	NM_003255.5	MANE Select	c.131-5263T>C		intron	N/A	NP_003246.1	P16035

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.131-5263T>C		intron	N/A	ENSP00000262768.6	P16035
	TIMP2	ENST00000970519.1		c.131-21536T>C		intron	N/A	ENSP00000640578.1
	TIMP2	ENST00000536189.6	TSL:2	c.-101-5263T>C		intron	N/A	ENSP00000441724.1	B4DFW2

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142484 AN: 152186 Hom.: 66838 Cov.: 33

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.936 AC: 142608 AN: 152304 Hom.: 66900 Cov.: 33 AF XY: 0.934 AC XY: 69548 AN XY: 74470

African (AFR) AF: 0.981 AC: 40785 AN: 41582

American (AMR) AF: 0.940 AC: 14386 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3330 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4239 AN: 5150

South Asian (SAS) AF: 0.790 AC: 3810 AN: 4824

European-Finnish (FIN) AF: 0.935 AC: 9926 AN: 10618

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63104 AN: 68032

Other (OTH) AF: 0.924 AC: 1951 AN: 2112

Alfa AF: 0.934 Hom.: 3965

Bravo AF: 0.941

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.39
DANN	Benign	0.31
PhyloP100		-3.3
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: rs4796813; hg19: chr17-76875264;