17-78875556-G-T

Variant names:

• chr17-78875556-G-T
• rs7218237
• NM_003255.5:c.131-1637C>A

Variant summary

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

The NM_003255.5(TIMP2):​c.131-1637C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,132 control chromosomes in the GnomAD database, including 766 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 0.089 (766 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-1637C>A		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.131-1637C>A		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-101-1637C>A		intron_variant	Intron 1 of 4	2		ENSP00000441724.1
TIMP2	ENST00000586713.6	c.-101-1637C>A		intron_variant	Intron 3 of 6	3		ENSP00000465968.2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13491 AN: 152012 Hom.: 767 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0854

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

GnomAD4 genome AF: 0.0886 AC: 13483 AN: 152132 Hom.: 766 Cov.: 32 AF XY: 0.0868 AC XY: 6456 AN XY: 74358

African (AFR) AF: 0.0294 AC: 1220 AN: 41516

American (AMR) AF: 0.0841 AC: 1286 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 295 AN: 3468

East Asian (EAS) AF: 0.0847 AC: 438 AN: 5170

South Asian (SAS) AF: 0.0855 AC: 412 AN: 4818

European-Finnish (FIN) AF: 0.0900 AC: 951 AN: 10572

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8485 AN: 67990

Other (OTH) AF: 0.0850 AC: 179 AN: 2106

Alfa AF: 0.111 Hom.: 1851

Bravo AF: 0.0880

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.68
PhyloP100		0.45
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: rs7218237; hg19: chr17-76871638;