rs6416835

chr17-78913153-A-Gchr17-78913153-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.130+11806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,082 control chromosomes in the GnomAD database, including 28,320 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 0.61 (28320 hom., cov: 33)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMP2	NM_003255.5	c.130+11806T>C		intron_variant		ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMP2	ENST00000262768.11	c.130+11806T>C		intron_variant		1	NM_003255.5	P1
TIMP2	ENST00000536189.6	c.-102+9057T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92071 AN: 151964 Hom.: 28280 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.606 AC: 92162 AN: 152082 Hom.: 28320 Cov.: 33 AF XY: 0.604 AC XY: 44874 AN XY: 74320

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.605

Alfa AF: 0.579 Hom.: 22586

Bravo AF: 0.603

Asia WGS AF: 0.446 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.0
Dann	Benign	0.60

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: rs6416835; hg19: chr17-76909235;