rs996999

Variant names:

• chr11-102796332-C-T
• rs996999
• NM_002421.4:c.625+332G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-102796332-C-T
• chr11-102796332-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):​c.625+332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,180 control chromosomes in the GnomAD database, including 3,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3172 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.598
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-102796332-C-T is Benign according to our data. Variant chr11-102796332-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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.625+332G>A		intron	N/A	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.427+332G>A		intron	N/A	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.583+1108C>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.625+332G>A		intron	N/A	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.325-1692C>T		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.583+1108C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29308 AN: 152062 Hom.: 3153 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29353 AN: 152180 Hom.: 3172 Cov.: 33 AF XY: 0.196 AC XY: 14567 AN XY: 74394

African (AFR) AF: 0.135 AC: 5612 AN: 41526

American (AMR) AF: 0.235 AC: 3598 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2384 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10578

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13606 AN: 68004

Other (OTH) AF: 0.184 AC: 390 AN: 2114

Alfa AF: 0.192 Hom.: 395

Bravo AF: 0.194

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.36
PhyloP100		-0.60
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: rs996999; hg19: chr11-102667063;