11-102795585-T-C

Variant names:

• chr11-102795585-T-C
• rs470558
• NM_002421.4:c.648A>G

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.648A>G​(p.Ala216Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,654 control chromosomes in the GnomAD database, including 715,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68631 hom., cov: 31)
  • Exomes 𝑓: 0.94 (646820 hom.)
• Consequence: MMP1 NM_002421.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.36
• Publications: 39 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=-0.84).
• BP6: Variant 11-102795585-T-C is Benign according to our data. Variant chr11-102795585-T-C is described in ClinVar as Benign. ClinVar VariationId is 403092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.648A>G	p.Ala216Ala	synonymous_variant	Exon 5 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.450A>G	p.Ala150Ala	synonymous_variant	Exon 5 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.583+361T>C		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.648A>G	p.Ala216Ala	synonymous_variant	Exon 5 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144315 AN: 152090 Hom.: 68573 Cov.: 31

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.939

GnomAD2 exomes AF: 0.924 AC: 230883 AN: 249836 AF XY: 0.926

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.845

Gnomad ASJ exome AF: 0.928

Gnomad EAS exome AF: 0.886

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.952

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.941 AC: 1373872 AN: 1460448 Hom.: 646820 Cov.: 42 AF XY: 0.940 AC XY: 682628 AN XY: 726446

African (AFR) AF: 0.991 AC: 33138 AN: 33424

American (AMR) AF: 0.852 AC: 37783 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 24252 AN: 26102

East Asian (EAS) AF: 0.884 AC: 35096 AN: 39686

South Asian (SAS) AF: 0.898 AC: 77098 AN: 85860

European-Finnish (FIN) AF: 0.927 AC: 49496 AN: 53370

Middle Eastern (MID) AF: 0.936 AC: 5388 AN: 5758

European-Non Finnish (NFE) AF: 0.949 AC: 1054967 AN: 1111538

Other (OTH) AF: 0.939 AC: 56654 AN: 60358

GnomAD4 genome AF: 0.949 AC: 144431 AN: 152206 Hom.: 68631 Cov.: 31 AF XY: 0.945 AC XY: 70339 AN XY: 74404

African (AFR) AF: 0.988 AC: 41044 AN: 41522

American (AMR) AF: 0.903 AC: 13814 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3197 AN: 3470

East Asian (EAS) AF: 0.894 AC: 4631 AN: 5178

South Asian (SAS) AF: 0.903 AC: 4351 AN: 4818

European-Finnish (FIN) AF: 0.917 AC: 9706 AN: 10588

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64584 AN: 68024

Other (OTH) AF: 0.940 AC: 1981 AN: 2108

Alfa AF: 0.945 Hom.: 102578

Bravo AF: 0.948

Asia WGS AF: 0.912 AC: 3173 AN: 3478

EpiCase AF: 0.947

EpiControl AF: 0.946

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-3.4
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: rs470558; hg19: chr11-102666316; COSMIC: COSV108129873;