rs5854

Variant names:

• chr11-102790143-G-A
• rs5854
• NM_002421.4:c.*269C>T

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.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 248,880 control chromosomes in the GnomAD database, including 12,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7104 hom., cov: 32)
  • Exomes 𝑓: 0.32 (5435 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.667
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-102790143-G-A is Benign according to our data. Variant chr11-102790143-G-A is described in ClinVar as Benign. ClinVar VariationId is 1267876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.*269C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.*269C>T		3_prime_UTR_variant	Exon 10 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.390-3002G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*269C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44596 AN: 151810 Hom.: 7109 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.323 AC: 31293 AN: 96954 Hom.: 5435 Cov.: 0 AF XY: 0.321 AC XY: 16061 AN XY: 50080

African (AFR) AF: 0.220 AC: 589 AN: 2676

American (AMR) AF: 0.227 AC: 801 AN: 3530

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1258 AN: 3314

East Asian (EAS) AF: 0.126 AC: 838 AN: 6666

South Asian (SAS) AF: 0.302 AC: 1597 AN: 5294

European-Finnish (FIN) AF: 0.304 AC: 1876 AN: 6162

Middle Eastern (MID) AF: 0.313 AC: 158 AN: 504

European-Non Finnish (NFE) AF: 0.355 AC: 22302 AN: 62772

Other (OTH) AF: 0.310 AC: 1874 AN: 6036

GnomAD4 genome AF: 0.294 AC: 44592 AN: 151926 Hom.: 7104 Cov.: 32 AF XY: 0.287 AC XY: 21327 AN XY: 74254

African (AFR) AF: 0.215 AC: 8910 AN: 41434

American (AMR) AF: 0.240 AC: 3659 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.0839 AC: 433 AN: 5160

South Asian (SAS) AF: 0.319 AC: 1534 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3034 AN: 10530

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24715 AN: 67946

Other (OTH) AF: 0.285 AC: 599 AN: 2104

Alfa AF: 0.324 Hom.: 2845

Bravo AF: 0.283

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		-0.67
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: rs5854; hg19: chr11-102660874;