11-102725749-A-G

Variant names:

• chr11-102725749-A-G
• rs11225395
• ENST00000528662.6:n.-148-746T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528662.6(MMP8):​n.-148-746T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,146 control chromosomes in the GnomAD database, including 30,409 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 0.63 (30409 hom., cov: 32)
• Consequence: MMP8 ENST00000528662.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 119 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000528662.6	n.-148-746T>C		intron_variant	Intron 1 of 11	5		ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95216 AN: 152028 Hom.: 30388 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.626 AC: 95272 AN: 152146 Hom.: 30409 Cov.: 32 AF XY: 0.628 AC XY: 46703 AN XY: 74372

African (AFR) AF: 0.756 AC: 31397 AN: 41518

American (AMR) AF: 0.586 AC: 8963 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2104 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3270 AN: 5156

South Asian (SAS) AF: 0.630 AC: 3033 AN: 4818

European-Finnish (FIN) AF: 0.610 AC: 6456 AN: 10586

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37952 AN: 67988

Other (OTH) AF: 0.635 AC: 1342 AN: 2112

Alfa AF: 0.621 Hom.: 6995

Bravo AF: 0.629

Asia WGS AF: 0.662 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.062

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11225395; hg19: chr11-102596480;