chr11-102523293-G-A

Position:

• chr11-102523293-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000260227.5(MMP7):​c.722C>T​(p.Pro241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,611,450 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (44 hom.)
• Consequence: MMP7 ENST00000260227.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.757

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039375424).
• BP6: Variant 11-102523293-G-A is Benign according to our data. Variant chr11-102523293-G-A is described in ClinVar as [Benign]. Clinvar id is 768477.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1886/152026) while in subpopulation AFR AF= 0.0433 (1793/41448). AF 95% confidence interval is 0.0416. There are 41 homozygotes in gnomad4. There are 903 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1886 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP7	NM_002423.5	c.722C>T	p.Pro241Leu	missense_variant	5/6	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.722C>T	p.Pro241Leu	missense_variant	5/6	1	NM_002423.5	ENSP00000260227	P1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1882 AN: 151908 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00816

GnomAD3 exomes AF: 0.00316 AC: 795 AN: 251216 Hom.: 13 AF XY: 0.00239 AC XY: 324 AN XY: 135782

Gnomad AFR exome AF: 0.0428

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00124 AC: 1812 AN: 1459424 Hom.: 44 Cov.: 30 AF XY: 0.00110 AC XY: 799 AN XY: 726014

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.00266

GnomAD4 genome AF: 0.0124 AC: 1886 AN: 152026 Hom.: 41 Cov.: 32 AF XY: 0.0122 AC XY: 903 AN XY: 74314

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.00472

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00807

Alfa AF: 0.00241 Hom.: 5

Bravo AF: 0.0142

ESP6500AA AF: 0.0393 AC: 173

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00371 AC: 450

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.2
DANN	Benign	0.32
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.057
Sift	Benign	1.0	T
Sift4G	Benign	0.13	T
Polyphen		0.016	B
Vest4		0.071
MVP		0.40
MPC		0.028
ClinPred		0.026	T
GERP RS		-1.7
Varity_R		0.14
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs17886506; hg19: chr11-102394024; COSMIC: COSV99036365; COSMIC: COSV99036365;