11-102724935-C-G

Position:

• chr11-102724935-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002424.3(MMP8):​c.-80G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,500,246 control chromosomes in the GnomAD database, including 632,405 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 0.92 (65150 hom., cov: 32)
  • Exomes 𝑓: 0.92 (567255 hom.)
• Consequence: MMP8 NM_002424.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.-80G>C		5_prime_UTR_variant	1/10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.-80G>C		5_prime_UTR_variant	1/10	1	NM_002424.3	ENSP00000236826.3

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140703 AN: 152186 Hom.: 65092 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.928

GnomAD4 exome AF: 0.917 AC: 1236261 AN: 1347942 Hom.: 567255 Cov.: 26 AF XY: 0.917 AC XY: 608128 AN XY: 662836

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.895

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.921

GnomAD4 genome AF: 0.925 AC: 140820 AN: 152304 Hom.: 65150 Cov.: 32 AF XY: 0.926 AC XY: 68926 AN XY: 74470

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.928

Alfa AF: 0.904 Hom.: 3447

Bravo AF: 0.926

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.084
DANN	Benign	0.37

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: rs2155052; hg19: chr11-102595666;