rs2071230

Variant names:

• chr11-102790228-A-G
• rs2071230
• NM_002421.4:c.*184T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-102790228-A-G
• chr11-102790228-A-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.*184T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 432,802 control chromosomes in the GnomAD database, including 4,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2534 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2243 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238
• Publications: 25 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 11-102790228-A-G is Benign according to our data. Variant chr11-102790228-A-G is described in ClinVar as Benign. ClinVar VariationId is 1255299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.*184T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.*184T>C		3_prime_UTR_variant	Exon 10 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.390-2917A>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*184T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23339 AN: 152064 Hom.: 2531 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.105 AC: 29551 AN: 280620 Hom.: 2243 Cov.: 4 AF XY: 0.105 AC XY: 15363 AN XY: 146038

African (AFR) AF: 0.279 AC: 2029 AN: 7268

American (AMR) AF: 0.190 AC: 1742 AN: 9192

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 1394 AN: 9098

East Asian (EAS) AF: 0.241 AC: 4982 AN: 20682

South Asian (SAS) AF: 0.111 AC: 1963 AN: 17760

European-Finnish (FIN) AF: 0.0419 AC: 934 AN: 22312

Middle Eastern (MID) AF: 0.169 AC: 223 AN: 1318

European-Non Finnish (NFE) AF: 0.0805 AC: 14172 AN: 175962

Other (OTH) AF: 0.124 AC: 2112 AN: 17028

GnomAD4 genome AF: 0.154 AC: 23365 AN: 152182 Hom.: 2534 Cov.: 33 AF XY: 0.154 AC XY: 11452 AN XY: 74420

African (AFR) AF: 0.279 AC: 11586 AN: 41476

American (AMR) AF: 0.202 AC: 3081 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5170

South Asian (SAS) AF: 0.125 AC: 602 AN: 4826

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10620

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5404 AN: 68012

Other (OTH) AF: 0.171 AC: 361 AN: 2116

Alfa AF: 0.111 Hom.: 3588

Bravo AF: 0.172

Asia WGS AF: 0.217 AC: 755 AN: 3478

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	-0.82
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		-0.24
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: rs2071230; hg19: chr11-102660959;