rs680753

Variant names:

• chr11-102840850-C-G
• rs680753
• NM_002422.5:c.626-257G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-102840850-C-G
• chr11-102840850-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002422.5(MMP3):​c.626-257G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,786 control chromosomes in the GnomAD database, including 1,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.11 (1252 hom., cov: 32)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.666
• Publications: 8 publications found

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-102840850-C-G is Benign according to our data. Variant chr11-102840850-C-G is described in ClinVar as Benign. ClinVar VariationId is 1245698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.626-257G>C		intron_variant	Intron 4 of 9	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.626-257G>C		intron_variant	Intron 4 of 9	1	NM_002422.5	ENSP00000299855.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16456 AN: 151668 Hom.: 1252 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.108 AC: 16457 AN: 151786 Hom.: 1252 Cov.: 32 AF XY: 0.112 AC XY: 8341 AN XY: 74158

African (AFR) AF: 0.0371 AC: 1535 AN: 41396

American (AMR) AF: 0.0857 AC: 1306 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3464

East Asian (EAS) AF: 0.0725 AC: 373 AN: 5148

South Asian (SAS) AF: 0.0796 AC: 382 AN: 4802

European-Finnish (FIN) AF: 0.280 AC: 2933 AN: 10480

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9126 AN: 67946

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.126 Hom.: 184

Bravo AF: 0.0914

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.76
PhyloP100		-0.67
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: rs680753; hg19: chr11-102711581;