rs2071232

Variant names:

• chr11-102794938-T-C
• rs2071232
• NM_002421.4:c.899+236A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):​c.899+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,246 control chromosomes in the GnomAD database, including 3,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3200 hom., cov: 32)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-102794938-T-C is Benign according to our data. Variant chr11-102794938-T-C is described in CliVar as Benign. Clinvar id is 1234842.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102794938-T-C is described in CliVar as Benign. Clinvar id is 1234842.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102794938-T-C is described in CliVar as Benign. Clinvar id is 1234842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.899+236A>G		intron_variant	Intron 6 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.701+236A>G		intron_variant	Intron 6 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.507-210T>C		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.899+236A>G		intron_variant	Intron 6 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29426 AN: 152128 Hom.: 3181 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.194 AC: 29472 AN: 152246 Hom.: 3200 Cov.: 32 AF XY: 0.197 AC XY: 14631 AN XY: 74442

African (AFR) AF: 0.136 AC: 5643 AN: 41546

American (AMR) AF: 0.236 AC: 3617 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2397 AN: 5176

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4826

European-Finnish (FIN) AF: 0.193 AC: 2047 AN: 10604

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13648 AN: 68008

Other (OTH) AF: 0.185 AC: 391 AN: 2116

Alfa AF: 0.201 Hom.: 2330

Bravo AF: 0.195

Asia WGS AF: 0.288 AC: 1003 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

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	4.6
DANN	Benign	0.52
PhyloP100		-0.019
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: rs2071232; hg19: chr11-102665669;