rs2012390

Positions:

• chr11-102720046-G-A
• chr11-102720046-G-T

Variant summary

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

The NM_002424.3(MMP8):​c.622+1355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,094 control chromosomes in the GnomAD database, including 42,418 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 0.75 (42418 hom., cov: 32)
• Consequence: MMP8 NM_002424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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 = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP8	NM_002424.3	c.622+1355C>T		intron_variant		ENST00000236826.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP8	ENST00000236826.8	c.622+1355C>T		intron_variant		1	NM_002424.3	P1
MMP8	ENST00000438475.2	c.548+1355C>T		intron_variant		5
MMP8	ENST00000528662.6	c.*599+1355C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113379 AN: 151978 Hom.: 42410 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.751

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.746 AC: 113424 AN: 152094 Hom.: 42418 Cov.: 32 AF XY: 0.746 AC XY: 55477 AN XY: 74324

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.750

Alfa AF: 0.755 Hom.: 57212

Bravo AF: 0.742

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.69

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: rs2012390; hg19: chr11-102590777;