rs12365082

Variant names:

• chr11-102712101-T-A
• rs12365082
• NM_002424.3:c.*1247A>T

Variant summary

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

The NM_002424.3(MMP8):​c.*1247A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,232 control chromosomes in the GnomAD database, including 3,125 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 (3125 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MMP8 NM_002424.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.87).
• 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 rank	MANE	Protein	UniProt
MMP8	NM_002424.3	c.*1247A>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826	c.*1247A>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_002424.3	ENSP00000236826.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27158 AN: 152114 Hom.: 3122 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.162

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.178 AC: 27157 AN: 152232 Hom.: 3125 Cov.: 32 AF XY: 0.177 AC XY: 13179 AN XY: 74426

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.160

Alfa AF: 0.221 Hom.: 563

Bravo AF: 0.172

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.79

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: rs12365082; hg19: chr11-102582832;