chr11-102527941-T-G

Position:

chr11-102527941-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002423.5(MMP7):c.151A>C(p.Asn51His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,062 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 11 hom. )

Consequence

MMP7
NM_002423.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.213

Variant links:

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]

MMP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026924312).

BP6

Variant 11-102527941-T-G is Benign according to our data. Variant chr11-102527941-T-G is described in ClinVar as [Benign]. Clinvar id is 715307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (975/152302) while in subpopulation AFR AF= 0.0211 (877/41574). AF 95% confidence interval is 0.0199. There are 14 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 975 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP7	NM_002423.5 linkuse as main transcript	c.151A>C	p.Asn51His	missense_variant	2/6	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMP7	ENST00000260227.5 linkuse as main transcript	c.151A>C	p.Asn51His	missense_variant	2/6	1	NM_002423.5	ENSP00000260227	P1
MMP7	ENST00000531200.1 linkuse as main transcript	n.198A>C		non_coding_transcript_exon_variant	2/3	2
MMP7	ENST00000533366.5 linkuse as main transcript	n.201A>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00639

AC:

972

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

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:

0.0000147

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00171

AC:

430

AN:

251078

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.000701

AC:

1024

AN:

1461760

Hom.:

Cov.:

AF XY:

0.000601

AC XY:

437

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00640

AC:

975

AN:

152302

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

448

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00777

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.6

DANN

Benign

0.90

DEOGEN2

Benign

0.064

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.46

REVEL

Benign

0.0080

Sift

Benign

0.13

Sift4G

Benign

0.21

Polyphen

0.48

Vest4

0.11

MVP

0.37

MPC

0.049

ClinPred

0.00061

GERP RS

-0.78

Varity_R

0.14

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over