rs470215

Variant names:

• chr11-102790368-T-C
• rs470215
• NM_002421.4:c.*44A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-102790368-T-C
• chr11-102790368-T-A
• chr11-102790368-T-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.*44A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,185,778 control chromosomes in the GnomAD database, including 70,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8955 hom., cov: 33)
  • Exomes 𝑓: 0.34 (61990 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.215
• Publications: 27 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 11-102790368-T-C is Benign according to our data. Variant chr11-102790368-T-C is described in ClinVar as Benign. ClinVar VariationId is 1245928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	NM_002421.4	MANE Select	c.*44A>G		3_prime_UTR	Exon 10 of 10	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.*44A>G		3_prime_UTR	Exon 10 of 10	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.390-2777T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.*44A>G		3_prime_UTR	Exon 10 of 10	ENSP00000322788.6	P03956
	MMP1	ENST00000680179.1		n.632A>G		non_coding_transcript_exon	Exon 5 of 5
	MMP1	ENST00000681445.1		n.628A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51147 AN: 152012 Hom.: 8951 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.313 AC: 66843 AN: 213750 AF XY: 0.317

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.0828

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.341 AC: 352787 AN: 1033648 Hom.: 61990 Cov.: 13 AF XY: 0.341 AC XY: 180694 AN XY: 529690

African (AFR) AF: 0.362 AC: 8794 AN: 24274

American (AMR) AF: 0.225 AC: 8222 AN: 36614

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 8536 AN: 21830

East Asian (EAS) AF: 0.117 AC: 4381 AN: 37452

South Asian (SAS) AF: 0.318 AC: 22149 AN: 69726

European-Finnish (FIN) AF: 0.309 AC: 16023 AN: 51818

Middle Eastern (MID) AF: 0.314 AC: 1202 AN: 3830

European-Non Finnish (NFE) AF: 0.361 AC: 268236 AN: 742350

Other (OTH) AF: 0.333 AC: 15244 AN: 45754

GnomAD4 genome AF: 0.336 AC: 51178 AN: 152130 Hom.: 8955 Cov.: 33 AF XY: 0.329 AC XY: 24456 AN XY: 74388

African (AFR) AF: 0.362 AC: 15022 AN: 41494

American (AMR) AF: 0.259 AC: 3964 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.0844 AC: 438 AN: 5190

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4814

European-Finnish (FIN) AF: 0.288 AC: 3051 AN: 10576

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24770 AN: 67990

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.340 Hom.: 7599

Bravo AF: 0.333

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		0.21
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: rs470215; hg19: chr11-102661099; COSMIC: COSV59512243;