11-102797291-C-T

Variant names:

• chr11-102797291-C-T
• rs10488
• NM_002421.4:c.315G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002421.4(MMP1):​c.315G>A​(p.Gly105Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,614,104 control chromosomes in the GnomAD database, including 3,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (654 hom., cov: 33)
  • Exomes 𝑓: 0.061 (3133 hom.)
• Consequence: MMP1 NM_002421.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.475
• Publications: 23 publications found

Genes affected

MMP1 (HGNC:7155): (matrix metallopeptidase 1) 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 the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

WTAPP1 (HGNC:):

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 11-102797291-C-T is Benign according to our data. Variant chr11-102797291-C-T is described in ClinVar as Benign. ClinVar VariationId is 403093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.475 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.315G>A	p.Gly105Gly	synonymous_variant	Exon 2 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.117G>A	p.Gly39Gly	synonymous_variant	Exon 2 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.584-733C>T		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.315G>A	p.Gly105Gly	synonymous_variant	Exon 2 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12350 AN: 152136 Hom.: 654 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0712

GnomAD2 exomes AF: 0.0568 AC: 14270 AN: 251138 AF XY: 0.0549

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0429

Gnomad ASJ exome AF: 0.0343

Gnomad EAS exome AF: 0.0181

Gnomad FIN exome AF: 0.0742

Gnomad NFE exome AF: 0.0592

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0615 AC: 89865 AN: 1461850 Hom.: 3133 Cov.: 32 AF XY: 0.0604 AC XY: 43903 AN XY: 727222

African (AFR) AF: 0.155 AC: 5174 AN: 33478

American (AMR) AF: 0.0442 AC: 1975 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 873 AN: 26134

East Asian (EAS) AF: 0.0121 AC: 479 AN: 39700

South Asian (SAS) AF: 0.0348 AC: 3003 AN: 86258

European-Finnish (FIN) AF: 0.0741 AC: 3956 AN: 53420

Middle Eastern (MID) AF: 0.0257 AC: 148 AN: 5766

European-Non Finnish (NFE) AF: 0.0636 AC: 70772 AN: 1111996

Other (OTH) AF: 0.0577 AC: 3485 AN: 60396

GnomAD4 genome AF: 0.0812 AC: 12357 AN: 152254 Hom.: 654 Cov.: 33 AF XY: 0.0787 AC XY: 5862 AN XY: 74462

African (AFR) AF: 0.143 AC: 5957 AN: 41534

American (AMR) AF: 0.0471 AC: 721 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.0156 AC: 81 AN: 5186

South Asian (SAS) AF: 0.0297 AC: 143 AN: 4820

European-Finnish (FIN) AF: 0.0706 AC: 749 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0630 AC: 4284 AN: 68022

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.0658 Hom.: 695

Bravo AF: 0.0825

Asia WGS AF: 0.0330 AC: 114 AN: 3478

EpiCase AF: 0.0554

EpiControl AF: 0.0546

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.4
DANN	Benign	0.71
PhyloP100		-0.47
Mutation Taster		=100/0	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: rs10488; hg19: chr11-102668022; COSMIC: COSV107318760;