11-102724935-C-T

Variant names:

• chr11-102724935-C-T
• rs2155052
• NM_002424.3:c.-80G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002424.3(MMP8):​c.-80G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP8 NM_002424.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 31 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.-80G>A		5_prime_UTR	Exon 1 of 10	NP_002415.1
	MMP8	NM_001304441.2		c.-240G>A		5_prime_UTR	Exon 1 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.-237G>A		5_prime_UTR	Exon 1 of 11	NP_001291371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.-80G>A		5_prime_UTR	Exon 1 of 10	ENSP00000236826.3
	MMP8	ENST00000528662.6	TSL:5	n.-80G>A		non_coding_transcript_exon	Exon 2 of 12	ENSP00000431431.2
	MMP8	ENST00000531168.1	TSL:3	n.-80G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000433812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000148 AC: 2 AN: 1348906 Hom.: 0 Cov.: 26 AF XY: 0.00000151 AC XY: 1 AN XY: 663300

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30440

American (AMR) AF: 0.00 AC: 0 AN: 33410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21822

East Asian (EAS) AF: 0.00 AC: 0 AN: 37440

South Asian (SAS) AF: 0.00 AC: 0 AN: 66750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5276

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1049816

Other (OTH) AF: 0.00 AC: 0 AN: 55042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3447

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.44
PhyloP100		-2.3
PromoterAI		-0.15	Neutral

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

Other links and lift over

dbSNP: rs2155052; hg19: chr11-102595666;