11-102797291-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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:44115): (WTAP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -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 id 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
WTAPP1	ENST00000371455.7	n.325-733C>T		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000525739.6	n.584-733C>T		intron_variant	Intron 3 of 7	2
WTAPP1	ENST00000544704.1	n.345-733C>T		intron_variant	Intron 1 of 3	4

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

GnomAD3 exomes AF: 0.0568 AC: 14270 AN: 251138 Hom.: 498 AF XY: 0.0549 AC XY: 7447 AN XY: 135716

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 SAS exome AF: 0.0350

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

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.0334

Gnomad4 EAS exome AF: 0.0121

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.0636

Gnomad4 OTH exome AF: 0.0577

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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0630

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0638 Hom.: 476

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

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: rs10488; hg19: chr11-102668022;