chr11-102713404-G-A

Variant names:

• chr11-102713404-G-A
• rs35231465
• NM_002424.3:c.1348C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002424.3(MMP8):​c.1348C>T​(p.Gln450*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,613,238 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (38 hom., cov: 33)
  • Exomes 𝑓: 0.021 (404 hom.)
• Consequence: MMP8 NM_002424.3 stop_gained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.07
• Publications: 24 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 -16 ACMG points.

• BP6: Variant 11-102713404-G-A is Benign according to our data. Variant chr11-102713404-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 403101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2340/152260) while in subpopulation NFE AF = 0.0244 (1662/68010). AF 95% confidence interval is 0.0235. There are 38 homozygotes in GnomAd4. There are 1075 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.1348C>T	p.Gln450*	stop_gained	Exon 10 of 10	NP_002415.1
	MMP8	NM_001304441.2		c.1279C>T	p.Gln427*	stop_gained	Exon 11 of 11	NP_001291370.1
	MMP8	NM_001304442.2		c.1279C>T	p.Gln427*	stop_gained	Exon 11 of 11	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.1348C>T	p.Gln450*	stop_gained	Exon 10 of 10	ENSP00000236826.3
	MMP8	ENST00000438475.2	TSL:5	c.*87C>T		3_prime_UTR	Exon 9 of 9	ENSP00000401004.2
	MMP8	ENST00000528662.6	TSL:5	n.*1325C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2340 AN: 152142 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.00490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0163 AC: 4086 AN: 250812 AF XY: 0.0165

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.0122

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0163

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0200

GnomAD4 exome AF: 0.0212 AC: 30974 AN: 1460978 Hom.: 404 Cov.: 31 AF XY: 0.0207 AC XY: 15051 AN XY: 726828

African (AFR) AF: 0.00275 AC: 92 AN: 33444

American (AMR) AF: 0.0127 AC: 569 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 519 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.00129 AC: 111 AN: 86242

European-Finnish (FIN) AF: 0.0174 AC: 927 AN: 53400

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5768

European-Non Finnish (NFE) AF: 0.0248 AC: 27580 AN: 1111280

Other (OTH) AF: 0.0185 AC: 1116 AN: 60360

GnomAD4 genome AF: 0.0154 AC: 2340 AN: 152260 Hom.: 38 Cov.: 33 AF XY: 0.0144 AC XY: 1075 AN XY: 74434

African (AFR) AF: 0.00488 AC: 203 AN: 41564

American (AMR) AF: 0.0146 AC: 223 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1662 AN: 68010

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0220 Hom.: 150

Bravo AF: 0.0156

TwinsUK AF: 0.0259 AC: 96

ALSPAC AF: 0.0304 AC: 117

ESP6500AA AF: 0.00454 AC: 20

ESP6500EA AF: 0.0226 AC: 194

ExAC AF: 0.0161 AC: 1950

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0251

EpiControl AF: 0.0254

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	35
DANN	Benign	0.73
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.095	N
PhyloP100		2.1
Vest4		0.67
GERP RS		-2.5
Mutation Taster		=165/35	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: rs35231465; hg19: chr11-102584135; COSMIC: COSV107247704;