rs5031036

Variant names:

• chr11-102795433-T-C
• rs5031036
• NM_002421.4:c.781+19A>G

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.781+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,610,094 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (773 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3270 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.468
• Publications: 15 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=-0.81).
• BP6: Variant 11-102795433-T-C is Benign according to our data. Variant chr11-102795433-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.781+19A>G		intron_variant	Intron 5 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.583+19A>G		intron_variant	Intron 5 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.583+209T>C		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.781+19A>G		intron_variant	Intron 5 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 13090 AN: 152098 Hom.: 773 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0736

GnomAD2 exomes AF: 0.0577 AC: 14266 AN: 247070 AF XY: 0.0556

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0432

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.0107

Gnomad FIN exome AF: 0.0744

Gnomad NFE exome AF: 0.0595

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0622 AC: 90725 AN: 1457878 Hom.: 3270 Cov.: 34 AF XY: 0.0611 AC XY: 44275 AN XY: 725030

African (AFR) AF: 0.174 AC: 5781 AN: 33244

American (AMR) AF: 0.0443 AC: 1946 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 862 AN: 25890

East Asian (EAS) AF: 0.00857 AC: 340 AN: 39662

South Asian (SAS) AF: 0.0349 AC: 2979 AN: 85480

European-Finnish (FIN) AF: 0.0741 AC: 3951 AN: 53310

Middle Eastern (MID) AF: 0.0267 AC: 153 AN: 5738

European-Non Finnish (NFE) AF: 0.0641 AC: 71131 AN: 1110496

Other (OTH) AF: 0.0595 AC: 3582 AN: 60176

GnomAD4 genome AF: 0.0861 AC: 13103 AN: 152216 Hom.: 773 Cov.: 32 AF XY: 0.0833 AC XY: 6204 AN XY: 74444

African (AFR) AF: 0.161 AC: 6693 AN: 41504

American (AMR) AF: 0.0481 AC: 736 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5190

South Asian (SAS) AF: 0.0302 AC: 146 AN: 4830

European-Finnish (FIN) AF: 0.0704 AC: 746 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4302 AN: 68006

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0712 Hom.: 193

Bravo AF: 0.0876

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 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	-0.81
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		0.47
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: rs5031036; hg19: chr11-102666164;