11-102843046-G-C

Variant names:

• chr11-102843046-G-C
• rs678815
• NM_002422.5:c.106-130C>G

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.106-130C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 798,894 control chromosomes in the GnomAD database, including 111,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25092 hom., cov: 30)
  • Exomes 𝑓: 0.51 (86736 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.48
• Publications: 22 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=-0.88).
• BP6: Variant 11-102843046-G-C is Benign according to our data. Variant chr11-102843046-G-C is described in ClinVar as Benign. ClinVar VariationId is 1262266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.106-130C>G		intron_variant	Intron 1 of 9	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.106-130C>G		intron_variant	Intron 1 of 9	1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000524478.1	n.77-130C>G		intron_variant	Intron 1 of 3	4		ENSP00000435255.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86293 AN: 151444 Hom.: 25054 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.509 AC: 329405 AN: 647334 Hom.: 86736 AF XY: 0.515 AC XY: 168825 AN XY: 327622

African (AFR) AF: 0.635 AC: 9834 AN: 15490

American (AMR) AF: 0.663 AC: 10595 AN: 15976

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 8657 AN: 14342

East Asian (EAS) AF: 0.681 AC: 21109 AN: 31008

South Asian (SAS) AF: 0.670 AC: 27458 AN: 40994

European-Finnish (FIN) AF: 0.577 AC: 16890 AN: 29274

Middle Eastern (MID) AF: 0.593 AC: 1482 AN: 2498

European-Non Finnish (NFE) AF: 0.464 AC: 216379 AN: 465990

Other (OTH) AF: 0.535 AC: 17001 AN: 31762

GnomAD4 genome AF: 0.570 AC: 86385 AN: 151560 Hom.: 25092 Cov.: 30 AF XY: 0.579 AC XY: 42852 AN XY: 74018

African (AFR) AF: 0.634 AC: 26187 AN: 41292

American (AMR) AF: 0.635 AC: 9677 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2132 AN: 3460

East Asian (EAS) AF: 0.674 AC: 3474 AN: 5156

South Asian (SAS) AF: 0.698 AC: 3349 AN: 4800

European-Finnish (FIN) AF: 0.607 AC: 6334 AN: 10440

Middle Eastern (MID) AF: 0.562 AC: 163 AN: 290

European-Non Finnish (NFE) AF: 0.492 AC: 33371 AN: 67870

Other (OTH) AF: 0.555 AC: 1167 AN: 2104

Alfa AF: 0.397 Hom.: 1162

Bravo AF: 0.574

Asia WGS AF: 0.666 AC: 2314 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	-0.88
CADD	Benign	0.024
DANN	Benign	0.59
PhyloP100		-1.5
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: rs678815; hg19: chr11-102713777;