11-102721263-A-T

Position:

• chr11-102721263-A-T

Variant summary

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

The ENST00000236826.8(MMP8):​c.622+138T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,249,360 control chromosomes in the GnomAD database, including 39,759 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 (3071 hom., cov: 32)
  • Exomes 𝑓: 0.25 (36688 hom.)
• Consequence: MMP8 ENST00000236826.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.622+138T>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.622+138T>A		intron_variant		1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2	c.548+138T>A		intron_variant		5		ENSP00000401004
MMP8	ENST00000528662.6	c.*599+138T>A		intron_variant, NMD_transcript_variant		5		ENSP00000431431

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27130 AN: 151902 Hom.: 3068 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.251 AC: 275283 AN: 1097340 Hom.: 36688 AF XY: 0.249 AC XY: 134788 AN XY: 541872

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0743

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.178 AC: 27132 AN: 152020 Hom.: 3071 Cov.: 32 AF XY: 0.177 AC XY: 13157 AN XY: 74306

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.172

Alfa AF: 0.212 Hom.: 508

Bravo AF: 0.173

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.50

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: rs1892886; hg19: chr11-102591994;