rs7503726

Positions:

• chr17-78925349-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003255.5(TIMP2):​c.-261A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 150,754 control chromosomes in the GnomAD database, including 31,103 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 0.64 (30948 hom., cov: 30)
  • Exomes 𝑓: 0.59 (155 hom.)
• Consequence: TIMP2 NM_003255.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMP2	NM_003255.5	c.-261A>G		5_prime_UTR_variant	1/5	ENST00000262768.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMP2	ENST00000262768.11	c.-261A>G		5_prime_UTR_variant	1/5	1	NM_003255.5	P1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 95700 AN: 149822 Hom.: 30928 Cov.: 30

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.587 AC: 485 AN: 826 Hom.: 155 Cov.: 0 AF XY: 0.606 AC XY: 241 AN XY: 398

Gnomad4 SAS exome AF: 0.585

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.639 AC: 95760 AN: 149928 Hom.: 30948 Cov.: 30 AF XY: 0.641 AC XY: 46851 AN XY: 73106

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.645

Alfa AF: 0.628 Hom.: 3683

Bravo AF: 0.632

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7503726; hg19: chr17-76921431;