rs491152

Variant names:

• chr11-102795312-A-G
• rs491152
• NM_002421.4:c.782-21T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-102795312-A-G
• chr11-102795312-A-C
• chr11-102795312-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.782-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,611,958 control chromosomes in the GnomAD database, including 715,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68669 hom., cov: 33)
  • Exomes 𝑓: 0.94 (646356 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.366
• Publications: 14 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=-0.85).
• BP6: Variant 11-102795312-A-G is Benign according to our data. Variant chr11-102795312-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 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.782-21T>C		intron	N/A	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.584-21T>C		intron	N/A	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.583+88A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.782-21T>C		intron	N/A	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.325-2712A>G		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.583+88A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144395 AN: 152172 Hom.: 68611 Cov.: 33

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.939

GnomAD2 exomes AF: 0.924 AC: 230705 AN: 249776 AF XY: 0.925

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.844

Gnomad ASJ exome AF: 0.928

Gnomad EAS exome AF: 0.885

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.952

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.941 AC: 1372997 AN: 1459668 Hom.: 646356 Cov.: 34 AF XY: 0.940 AC XY: 682378 AN XY: 726276

African (AFR) AF: 0.991 AC: 33124 AN: 33410

American (AMR) AF: 0.851 AC: 37957 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 24260 AN: 26112

East Asian (EAS) AF: 0.884 AC: 35085 AN: 39684

South Asian (SAS) AF: 0.898 AC: 77358 AN: 86188

European-Finnish (FIN) AF: 0.927 AC: 49457 AN: 53334

Middle Eastern (MID) AF: 0.936 AC: 5388 AN: 5758

European-Non Finnish (NFE) AF: 0.949 AC: 1053770 AN: 1110288

Other (OTH) AF: 0.939 AC: 56598 AN: 60298

GnomAD4 genome AF: 0.949 AC: 144512 AN: 152290 Hom.: 68669 Cov.: 33 AF XY: 0.945 AC XY: 70395 AN XY: 74462

African (AFR) AF: 0.989 AC: 41078 AN: 41554

American (AMR) AF: 0.903 AC: 13818 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3199 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4633 AN: 5184

South Asian (SAS) AF: 0.903 AC: 4351 AN: 4816

European-Finnish (FIN) AF: 0.917 AC: 9726 AN: 10606

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64600 AN: 68040

Other (OTH) AF: 0.939 AC: 1986 AN: 2114

Alfa AF: 0.947 Hom.: 13755

Bravo AF: 0.948

Asia WGS AF: 0.912 AC: 3173 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	-0.85
CADD	Benign	5.4
DANN	Benign	0.20
PhyloP100		-0.37
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: rs491152; hg19: chr11-102666043;