rs2239008

Variant names:

• chr11-102790349-G-A
• rs2239008
• NM_002421.4:c.*63C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102790349-G-A
• chr11-102790349-G-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.*63C>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 0.208 in 938,944 control chromosomes in the GnomAD database, including 22,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3180 hom., cov: 33)
  • Exomes 𝑓: 0.21 (18838 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0840
• Publications: 16 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=-0.82).
• BP6: Variant 11-102790349-G-A is Benign according to our data. Variant chr11-102790349-G-A is described in ClinVar as Benign. ClinVar VariationId is 1233849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.*63C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.*63C>T		3_prime_UTR_variant	Exon 10 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.390-2796G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*63C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29255 AN: 152012 Hom.: 3162 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.211 AC: 166113 AN: 786814 Hom.: 18838 Cov.: 10 AF XY: 0.210 AC XY: 86254 AN XY: 409922

African (AFR) AF: 0.126 AC: 2443 AN: 19416

American (AMR) AF: 0.261 AC: 7807 AN: 29908

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 2561 AN: 18644

East Asian (EAS) AF: 0.420 AC: 15053 AN: 35842

South Asian (SAS) AF: 0.218 AC: 12700 AN: 58342

European-Finnish (FIN) AF: 0.198 AC: 9885 AN: 49826

Middle Eastern (MID) AF: 0.153 AC: 453 AN: 2962

European-Non Finnish (NFE) AF: 0.201 AC: 107625 AN: 534526

Other (OTH) AF: 0.203 AC: 7586 AN: 37348

GnomAD4 genome AF: 0.193 AC: 29292 AN: 152130 Hom.: 3180 Cov.: 33 AF XY: 0.196 AC XY: 14544 AN XY: 74360

African (AFR) AF: 0.132 AC: 5470 AN: 41518

American (AMR) AF: 0.237 AC: 3625 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2386 AN: 5174

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2055 AN: 10580

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

European-Non Finnish (NFE) AF: 0.200 AC: 13617 AN: 67986

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.190 Hom.: 1228

Bravo AF: 0.194

Asia WGS AF: 0.283 AC: 985 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	-0.82
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		0.084
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: rs2239008; hg19: chr11-102661080; COSMIC: COSV59509723;