rs4796813

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-5263T>C		intron_variant		ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11	c.131-5263T>C		intron_variant		1	NM_003255.5	ENSP00000262768	P1
TIMP2	ENST00000536189.6	c.-101-5263T>C		intron_variant		2		ENSP00000441724
TIMP2	ENST00000586713.6	c.-101-5263T>C		intron_variant		3		ENSP00000465968

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

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.924

Alfa AF: 0.930 Hom.: 3592

Bravo AF: 0.941

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.39
DANN	Benign	0.31

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: rs4796813; hg19: chr17-76875264;