rs7342880

Variant names:

• chr17-78878430-A-C
• rs7342880
• NM_003255.5:c.131-4511T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-78878430-A-C
• chr17-78878430-A-G
• chr17-78878430-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.131-4511T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,194 control chromosomes in the GnomAD database, including 65,693 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 0.93 (65693 hom., cov: 31)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-4511T>G		intron_variant	Intron 1 of 4	ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11	c.131-4511T>G		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-101-4511T>G		intron_variant	Intron 1 of 4	2		ENSP00000441724.1
TIMP2	ENST00000586713.6	c.-101-4511T>G		intron_variant	Intron 3 of 6	3		ENSP00000465968.2

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141204 AN: 152076 Hom.: 65641 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.923

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

GnomAD4 genome AF: 0.929 AC: 141318 AN: 152194 Hom.: 65693 Cov.: 31 AF XY: 0.926 AC XY: 68939 AN XY: 74428

African (AFR) AF: 0.954 AC: 39593 AN: 41516

American (AMR) AF: 0.938 AC: 14338 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4237 AN: 5158

South Asian (SAS) AF: 0.788 AC: 3798 AN: 4822

European-Finnish (FIN) AF: 0.935 AC: 9919 AN: 10612

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63087 AN: 68018

Other (OTH) AF: 0.922 AC: 1943 AN: 2108

Alfa AF: 0.928 Hom.: 183364

Bravo AF: 0.932

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		-0.029
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: rs7342880; hg19: chr17-76874512;