11-102724935-C-G

Variant names:

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

Variant summary

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

The ENST00000236826.8(MMP8):​c.-80G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,500,246 control chromosomes in the GnomAD database, including 632,405 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 0.92 (65150 hom., cov: 32)
  • Exomes 𝑓: 0.92 (567255 hom.)
• Consequence: MMP8 ENST00000236826.8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000236826.8. 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>C		5_prime_UTR	Exon 1 of 10	NP_002415.1
	MMP8	NM_001304441.2		c.-240G>C		5_prime_UTR	Exon 1 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.-237G>C		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>C		5_prime_UTR	Exon 1 of 10	ENSP00000236826.3
	MMP8	ENST00000528662.6	TSL:5	n.-80G>C		non_coding_transcript_exon	Exon 2 of 12	ENSP00000431431.2
	MMP8	ENST00000531168.1	TSL:3	n.-80G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000433812.1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140703 AN: 152186 Hom.: 65092 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.928

GnomAD4 exome AF: 0.917 AC: 1236261 AN: 1347942 Hom.: 567255 Cov.: 26 AF XY: 0.917 AC XY: 608128 AN XY: 662836

African (AFR) AF: 0.920 AC: 27994 AN: 30418

American (AMR) AF: 0.952 AC: 31790 AN: 33394

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 19517 AN: 21796

East Asian (EAS) AF: 1.00 AC: 37433 AN: 37438

South Asian (SAS) AF: 0.937 AC: 62497 AN: 66712

European-Finnish (FIN) AF: 0.931 AC: 45510 AN: 48866

Middle Eastern (MID) AF: 0.926 AC: 4882 AN: 5274

European-Non Finnish (NFE) AF: 0.911 AC: 956003 AN: 1049044

Other (OTH) AF: 0.921 AC: 50635 AN: 55000

GnomAD4 genome AF: 0.925 AC: 140820 AN: 152304 Hom.: 65150 Cov.: 32 AF XY: 0.926 AC XY: 68926 AN XY: 74470

African (AFR) AF: 0.925 AC: 38447 AN: 41552

American (AMR) AF: 0.932 AC: 14270 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3089 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5183 AN: 5188

South Asian (SAS) AF: 0.940 AC: 4538 AN: 4828

European-Finnish (FIN) AF: 0.927 AC: 9836 AN: 10616

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62366 AN: 68030

Other (OTH) AF: 0.928 AC: 1959 AN: 2110

Alfa AF: 0.904 Hom.: 3447

Bravo AF: 0.926

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.084
DANN	Benign	0.37
PhyloP100		-2.3
PromoterAI		-0.16	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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;