rs11602288

Variant names:

• chr11-102721429-G-A
• rs11602288
• NM_002424.3:c.594C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102721429-G-A
• chr11-102721429-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002424.3(MMP8):​c.594C>T​(p.Ala198Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,613,442 control chromosomes in the GnomAD database, including 185 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 0.011 (18 hom., cov: 32)
  • Exomes 𝑓: 0.013 (167 hom.)
• Consequence: MMP8 NM_002424.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 8 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.668 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0107 (1632/151942) while in subpopulation SAS AF = 0.0245 (118/4808). AF 95% confidence interval is 0.0209. There are 18 homozygotes in GnomAd4. There are 826 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3	c.594C>T	p.Ala198Ala	synonymous_variant	Exon 4 of 10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.594C>T	p.Ala198Ala	synonymous_variant	Exon 4 of 10	1	NM_002424.3	ENSP00000236826.3

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1636 AN: 151824 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0134 AC: 3377 AN: 251324 AF XY: 0.0146

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00547

Gnomad ASJ exome AF: 0.0235

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0256

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0125 AC: 18296 AN: 1461500 Hom.: 167 Cov.: 33 AF XY: 0.0130 AC XY: 9481 AN XY: 727066

African (AFR) AF: 0.00197 AC: 66 AN: 33452

American (AMR) AF: 0.00609 AC: 272 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 571 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.0257 AC: 2220 AN: 86244

European-Finnish (FIN) AF: 0.0262 AC: 1399 AN: 53414

Middle Eastern (MID) AF: 0.0271 AC: 156 AN: 5764

European-Non Finnish (NFE) AF: 0.0115 AC: 12820 AN: 1111752

Other (OTH) AF: 0.0131 AC: 790 AN: 60378

GnomAD4 genome AF: 0.0107 AC: 1632 AN: 151942 Hom.: 18 Cov.: 32 AF XY: 0.0111 AC XY: 826 AN XY: 74254

African (AFR) AF: 0.00256 AC: 106 AN: 41430

American (AMR) AF: 0.0101 AC: 154 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4808

European-Finnish (FIN) AF: 0.0263 AC: 277 AN: 10532

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 861 AN: 67962

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.0114 Hom.: 3

Bravo AF: 0.00892

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0138

EpiControl AF: 0.0134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.9
DANN	Benign	0.53
PhyloP100		-0.67
Mutation Taster		=99/1	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: rs11602288; hg19: chr11-102592160; COSMIC: COSV52633777; COSMIC: COSV52633777;