11-102527862-C-T

Variant names:

• chr11-102527862-C-T
• rs10502001
• NM_002423.5:c.230G>A

Variant summary

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

The NM_002423.5(MMP7):​c.230G>A​(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,680 control chromosomes in the GnomAD database, including 37,027 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R77R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.16 (2529 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34498 hom.)
• Consequence: MMP7 NM_002423.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 53 publications found

Genes affected

MMP7 (HGNC:7174): (matrix metallopeptidase 7) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down proteoglycans, fibronectin, elastin and casein and differs from most MMP family members in that it lacks a conserved C-terminal hemopexin domain. The enzyme is involved in wound healing, and studies in mice suggest that it regulates the activity of defensins in intestinal mucosa. The gene is part of a cluster of MMP genes on chromosome 11. This gene exhibits elevated expression levels in multiple human cancers. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057508945).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP7	NM_002423.5	c.230G>A	p.Arg77His	missense_variant	Exon 2 of 6	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.230G>A	p.Arg77His	missense_variant	Exon 2 of 6	1	NM_002423.5	ENSP00000260227.4
MMP7	ENST00000531200.1	n.277G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2
MMP7	ENST00000533366.5	n.280G>A		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24957 AN: 151944 Hom.: 2528 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.188 AC: 47272 AN: 251434 AF XY: 0.187

Gnomad AFR exome AF: 0.0393

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.255

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.211 AC: 307798 AN: 1461618 Hom.: 34498 Cov.: 34 AF XY: 0.209 AC XY: 151721 AN XY: 727124

African (AFR) AF: 0.0326 AC: 1092 AN: 33480

American (AMR) AF: 0.157 AC: 6999 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6150 AN: 26128

East Asian (EAS) AF: 0.219 AC: 8698 AN: 39692

South Asian (SAS) AF: 0.0970 AC: 8370 AN: 86258

European-Finnish (FIN) AF: 0.236 AC: 12594 AN: 53406

Middle Eastern (MID) AF: 0.145 AC: 838 AN: 5768

European-Non Finnish (NFE) AF: 0.226 AC: 250961 AN: 1111772

Other (OTH) AF: 0.200 AC: 12096 AN: 60392

GnomAD4 genome AF: 0.164 AC: 24962 AN: 152062 Hom.: 2529 Cov.: 32 AF XY: 0.161 AC XY: 11981 AN XY: 74308

African (AFR) AF: 0.0400 AC: 1662 AN: 41520

American (AMR) AF: 0.164 AC: 2505 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1204 AN: 5178

South Asian (SAS) AF: 0.0924 AC: 445 AN: 4814

European-Finnish (FIN) AF: 0.214 AC: 2255 AN: 10554

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15526 AN: 67948

Other (OTH) AF: 0.175 AC: 369 AN: 2104

Alfa AF: 0.201 Hom.: 11409

Bravo AF: 0.156

TwinsUK AF: 0.230 AC: 851

ALSPAC AF: 0.231 AC: 891

ESP6500AA AF: 0.0461 AC: 203

ESP6500EA AF: 0.219 AC: 1884

ExAC AF: 0.185 AC: 22492

Asia WGS AF: 0.132 AC: 460 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.027
DANN	Benign	0.89
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.094	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.74	N
PhyloP100		-0.28
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.069
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.012	B
Vest4		0.029
MPC		0.031
ClinPred		0.0031	T
GERP RS		-7.8
Varity_R		0.051
gMVP		0.28
Mutation Taster		=86/14	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: rs10502001; hg19: chr11-102398593; COSMIC: COSV52771929;