rs7125320

Variant names:

• chr11-102792977-T-G
• rs7125320
• NM_002421.4:c.900-239A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002421.4(MMP1):​c.900-239A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,150 control chromosomes in the GnomAD database, including 1,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.12 (1390 hom., cov: 32)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-102792977-T-G is Benign according to our data. Variant chr11-102792977-T-G is described in ClinVar as Benign. ClinVar VariationId is 1175389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.900-239A>C		intron_variant	Intron 6 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.702-239A>C		intron_variant	Intron 6 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.390-168T>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.900-239A>C		intron_variant	Intron 6 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17883 AN: 152032 Hom.: 1386 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 17893 AN: 152150 Hom.: 1390 Cov.: 32 AF XY: 0.119 AC XY: 8856 AN XY: 74392

African (AFR) AF: 0.170 AC: 7049 AN: 41492

American (AMR) AF: 0.182 AC: 2777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3466

East Asian (EAS) AF: 0.246 AC: 1274 AN: 5182

South Asian (SAS) AF: 0.124 AC: 598 AN: 4816

European-Finnish (FIN) AF: 0.0356 AC: 377 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4925 AN: 68002

Other (OTH) AF: 0.144 AC: 304 AN: 2116

Alfa AF: 0.0869 Hom.: 698

Bravo AF: 0.130

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.074
DANN	Benign	0.65
PhyloP100		-1.5
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: rs7125320; hg19: chr11-102663708;