rs11654470

Variant names:

• chr17-78881249-T-C
• rs11654470
• NM_003255.5:c.131-7330A>G

Variant summary

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

The NM_003255.5(TIMP2):​c.131-7330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,262 control chromosomes in the GnomAD database, including 1,735 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 0.14 (1735 hom., cov: 34)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-7330A>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.131-7330A>G		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-101-7330A>G		intron_variant	Intron 1 of 4	2		ENSP00000441724.1
TIMP2	ENST00000586713.6	c.-101-7330A>G		intron_variant	Intron 3 of 6	3		ENSP00000465968.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21511 AN: 152144 Hom.: 1728 Cov.: 34

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.142 AC: 21552 AN: 152262 Hom.: 1735 Cov.: 34 AF XY: 0.143 AC XY: 10635 AN XY: 74442

African (AFR) AF: 0.176 AC: 7320 AN: 41560

American (AMR) AF: 0.112 AC: 1717 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1437 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1426 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7696 AN: 68010

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.124 Hom.: 2422

Bravo AF: 0.142

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.26
PhyloP100		-0.47
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: rs11654470; hg19: chr17-76877331;