rs2071231

Variant names:

• chr11-102790545-T-G
• rs2071231
• NM_002421.4:c.1301-24A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-102790545-T-G
• chr11-102790545-T-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002421.4(MMP1):​c.1301-24A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,422,984 control chromosomes in the GnomAD database, including 3,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.061 (634 hom., cov: 33)
  • Exomes 𝑓: 0.029 (2524 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0480
• Publications: 10 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 -16 ACMG points.

• BP6: Variant 11-102790545-T-G is Benign according to our data. Variant chr11-102790545-T-G is described in ClinVar as Benign. ClinVar VariationId is 1260456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 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.1301-24A>C		intron	N/A	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.1103-24A>C		intron	N/A	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.390-2600T>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.1301-24A>C		intron	N/A	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.325-7479T>G		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.390-2600T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9203 AN: 152162 Hom.: 630 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00964

Gnomad OTH AF: 0.0659

GnomAD2 exomes AF: 0.0691 AC: 14959 AN: 216484 AF XY: 0.0630

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.0465

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.000983

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0488

GnomAD4 exome AF: 0.0294 AC: 37404 AN: 1270704 Hom.: 2524 Cov.: 17 AF XY: 0.0305 AC XY: 19482 AN XY: 639520

African (AFR) AF: 0.116 AC: 3339 AN: 28768

American (AMR) AF: 0.152 AC: 5976 AN: 39432

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 1057 AN: 24128

East Asian (EAS) AF: 0.243 AC: 9355 AN: 38504

South Asian (SAS) AF: 0.0887 AC: 6900 AN: 77794

European-Finnish (FIN) AF: 0.00151 AC: 79 AN: 52332

Middle Eastern (MID) AF: 0.0632 AC: 324 AN: 5124

European-Non Finnish (NFE) AF: 0.00844 AC: 8022 AN: 950906

Other (OTH) AF: 0.0438 AC: 2352 AN: 53716

GnomAD4 genome AF: 0.0605 AC: 9216 AN: 152280 Hom.: 634 Cov.: 33 AF XY: 0.0633 AC XY: 4710 AN XY: 74450

African (AFR) AF: 0.112 AC: 4666 AN: 41538

American (AMR) AF: 0.111 AC: 1703 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 188 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5174

South Asian (SAS) AF: 0.100 AC: 485 AN: 4830

European-Finnish (FIN) AF: 0.00103 AC: 11 AN: 10628

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00964 AC: 656 AN: 68034

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0215 Hom.: 20

Bravo AF: 0.0711

Asia WGS AF: 0.194 AC: 673 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	-0.57
CADD	Benign	17
DANN	Benign	0.91
PhyloP100		0.048
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2071231; hg19: chr11-102661276;