NM_002421.4:c.831G>A

Variant names:

• chr11-102795242-C-T
• rs1051121
• NM_002421.4:c.831G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002421.4(MMP1):​c.831G>A​(p.Ala277Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,613,932 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (49 hom., cov: 33)
  • Exomes 𝑓: 0.028 (666 hom.)
• Consequence: MMP1 NM_002421.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 11-102795242-C-T is Benign according to our data. Variant chr11-102795242-C-T is described in ClinVar as Benign. ClinVar VariationId is 403091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 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.831G>A	p.Ala277Ala	synonymous	Exon 6 of 10	NP_002412.1
	MMP1	NM_001145938.2		c.633G>A	p.Ala211Ala	synonymous	Exon 6 of 10	NP_001139410.1
	WTAPP1	NR_038390.1		n.583+18C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.831G>A	p.Ala277Ala	synonymous	Exon 6 of 10	ENSP00000322788.6
	WTAPP1	ENST00000371455.7	TSL:4	n.325-2782C>T		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.583+18C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3162 AN: 152146 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00774

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0209 AC: 5230 AN: 250400 AF XY: 0.0221

Gnomad AFR exome AF: 0.00771

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0572

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00582

Gnomad NFE exome AF: 0.0294

Gnomad OTH exome AF: 0.0306

GnomAD4 exome AF: 0.0277 AC: 40535 AN: 1461668 Hom.: 666 Cov.: 30 AF XY: 0.0278 AC XY: 20204 AN XY: 727140

African (AFR) AF: 0.00783 AC: 262 AN: 33476

American (AMR) AF: 0.0173 AC: 772 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0575 AC: 1503 AN: 26130

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39696

South Asian (SAS) AF: 0.0111 AC: 960 AN: 86256

European-Finnish (FIN) AF: 0.00719 AC: 384 AN: 53382

Middle Eastern (MID) AF: 0.0640 AC: 369 AN: 5762

European-Non Finnish (NFE) AF: 0.0311 AC: 34581 AN: 1111874

Other (OTH) AF: 0.0280 AC: 1690 AN: 60386

GnomAD4 genome AF: 0.0208 AC: 3163 AN: 152264 Hom.: 49 Cov.: 33 AF XY: 0.0198 AC XY: 1471 AN XY: 74436

African (AFR) AF: 0.00736 AC: 306 AN: 41554

American (AMR) AF: 0.0245 AC: 374 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4822

European-Finnish (FIN) AF: 0.00774 AC: 82 AN: 10590

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2047 AN: 68028

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.0274 Hom.: 106

Bravo AF: 0.0210

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0324

EpiControl AF: 0.0343

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.1
DANN	Benign	0.61
PhyloP100		-1.2
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: rs1051121; hg19: chr11-102665973; COSMIC: COSV59512157;