chr17-78922049-T-G

Variant names:

• chr17-78922049-T-G
• rs7212662
• NM_003255.5:c.130+2910A>C

Variant summary

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

The NM_003255.5(TIMP2):​c.130+2910A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,374 control chromosomes in the GnomAD database, including 12,466 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 0.39 (12466 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.130+2910A>C		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.130+2910A>C		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-102+161A>C		intron_variant	Intron 1 of 4	2		ENSP00000441724.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59474 AN: 151264 Hom.: 12472 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.393 AC: 59472 AN: 151374 Hom.: 12466 Cov.: 32 AF XY: 0.398 AC XY: 29454 AN XY: 73944

African (AFR) AF: 0.252 AC: 10469 AN: 41468

American (AMR) AF: 0.403 AC: 6063 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1349 AN: 4868

South Asian (SAS) AF: 0.326 AC: 1526 AN: 4686

European-Finnish (FIN) AF: 0.567 AC: 5997 AN: 10574

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31037 AN: 67950

Other (OTH) AF: 0.410 AC: 862 AN: 2100

Alfa AF: 0.419 Hom.: 28376

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		-1.7
PromoterAI		-0.018	Neutral
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: rs7212662; hg19: chr17-76918131;