rs11225394

Positions:

• chr11-102724682-C-T

Variant summary

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

The NM_002424.3(MMP8):​c.102+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,314,524 control chromosomes in the GnomAD database, including 42,030 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 0.18 (3069 hom., cov: 33)
  • Exomes 𝑓: 0.25 (38961 hom.)
• Consequence: MMP8 NM_002424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.102+72G>A		intron_variant		ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.102+72G>A		intron_variant		1	NM_002424.3	ENSP00000236826.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27180 AN: 152030 Hom.: 3066 Cov.: 33

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.252 AC: 293140 AN: 1162374 Hom.: 38961 AF XY: 0.250 AC XY: 143827 AN XY: 576010

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.0764

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.179 AC: 27182 AN: 152150 Hom.: 3069 Cov.: 33 AF XY: 0.177 AC XY: 13179 AN XY: 74364

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0927

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.171

Alfa AF: 0.232 Hom.: 2067

Bravo AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.23

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: rs11225394; hg19: chr11-102595413;