rs3740938

chr11-102716331-G-Achr11-102716331-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002424.3(MMP8):c.873C>T(p.Leu291=) 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

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP8	NM_002424.3	c.873C>T	p.Leu291=	synonymous_variant	6/10	ENST00000236826.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP8	ENST00000236826.8	c.873C>T	p.Leu291=	synonymous_variant	6/10	1	NM_002424.3	P1
MMP8	ENST00000438475.2	c.801C>T	p.Leu267=	synonymous_variant	6/9	5
MMP8	ENST00000528662.6	c.*850C>T		3_prime_UTR_variant, NMD_transcript_variant	8/12	5

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

GnomAD3 exomes AF: 0.0973 AC: 24250 AN: 249108 Hom.: 1712 AF XY: 0.0973 AC XY: 13109 AN XY: 134668

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 SAS exome AF: 0.148

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

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.0884

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0733

Gnomad4 NFE exome AF: 0.0621

Gnomad4 OTH exome AF: 0.0788

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

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0887

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0658 Hom.: 613

Bravo AF: 0.0663

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	6.6
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740938; hg19: chr11-102587062; COSMIC: COSV52631649;