11-102716331-G-A

Variant names:

• chr11-102716331-G-A
• rs3740938
• NM_002424.3:c.873C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002424.3(MMP8):​c.873C>T​(p.Leu291Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,600,928 control chromosomes in the GnomAD database, including 5,870 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 0.067 (532 hom., cov: 30)
  • Exomes 𝑓: 0.074 (5338 hom.)
• Consequence: MMP8 NM_002424.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 29 publications found

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP7: Synonymous conserved (PhyloP=-0.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.873C>T	p.Leu291Leu	synonymous	Exon 6 of 10	NP_002415.1
	MMP8	NM_001304441.2		c.804C>T	p.Leu268Leu	synonymous	Exon 7 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.804C>T	p.Leu268Leu	synonymous	Exon 7 of 11	NP_001291371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.873C>T	p.Leu291Leu	synonymous	Exon 6 of 10	ENSP00000236826.3
	MMP8	ENST00000438475.2	TSL:5	c.798C>T	p.Leu266Leu	synonymous	Exon 6 of 9	ENSP00000401004.2
	MMP8	ENST00000528662.6	TSL:5	n.*850C>T		non_coding_transcript_exon	Exon 8 of 12	ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10159 AN: 150710 Hom.: 523 Cov.: 30

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0712

GnomAD2 exomes AF: 0.0973 AC: 24250 AN: 249108 AF XY: 0.0973

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.0921

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.0711

Gnomad NFE exome AF: 0.0633

Gnomad OTH exome AF: 0.0891

GnomAD4 exome AF: 0.0745 AC: 107987 AN: 1450102 Hom.: 5338 Cov.: 31 AF XY: 0.0764 AC XY: 55116 AN XY: 721526

African (AFR) AF: 0.0107 AC: 353 AN: 33032

American (AMR) AF: 0.153 AC: 6775 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 2279 AN: 25774

East Asian (EAS) AF: 0.221 AC: 8665 AN: 39128

South Asian (SAS) AF: 0.144 AC: 12371 AN: 85638

European-Finnish (FIN) AF: 0.0733 AC: 3867 AN: 52734

Middle Eastern (MID) AF: 0.0654 AC: 374 AN: 5716

European-Non Finnish (NFE) AF: 0.0621 AC: 68593 AN: 1104120

Other (OTH) AF: 0.0788 AC: 4710 AN: 59736

GnomAD4 genome AF: 0.0675 AC: 10179 AN: 150826 Hom.: 532 Cov.: 30 AF XY: 0.0706 AC XY: 5200 AN XY: 73610

African (AFR) AF: 0.0127 AC: 522 AN: 41064

American (AMR) AF: 0.116 AC: 1757 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 307 AN: 3460

East Asian (EAS) AF: 0.241 AC: 1222 AN: 5072

South Asian (SAS) AF: 0.154 AC: 730 AN: 4754

European-Finnish (FIN) AF: 0.0756 AC: 778 AN: 10286

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0679 AC: 4601 AN: 67802

Other (OTH) AF: 0.0733 AC: 154 AN: 2100

Alfa AF: 0.0653 Hom.: 760

Bravo AF: 0.0663

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.6
DANN	Benign	0.77
PhyloP100		-0.070
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: rs3740938; hg19: chr11-102587062; COSMIC: COSV52631649;