rs3213460

Variant names:

• chr11-102798151-G-A
• rs3213460
• NM_002421.4:c.-59C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102798151-G-A
• chr11-102798151-G-C

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.-59C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,399,982 control chromosomes in the GnomAD database, including 13,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1228 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12075 hom.)
• Consequence: MMP1 NM_002421.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.522
• Publications: 18 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=-0.8).
• BP6: Variant 11-102798151-G-A is Benign according to our data. Variant chr11-102798151-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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.-59C>T		5_prime_UTR	Exon 1 of 10	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.-105C>T		5_prime_UTR	Exon 1 of 10	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.682+29G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.-59C>T		5_prime_UTR	Exon 1 of 10	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.423+29G>A		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.682+29G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17399 AN: 152004 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.132 AC: 165217 AN: 1247860 Hom.: 12075 Cov.: 16 AF XY: 0.131 AC XY: 81669 AN XY: 624718

African (AFR) AF: 0.0537 AC: 1551 AN: 28868

American (AMR) AF: 0.0751 AC: 2700 AN: 35968

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3291 AN: 23362

East Asian (EAS) AF: 0.0439 AC: 1632 AN: 37206

South Asian (SAS) AF: 0.0716 AC: 5384 AN: 75188

European-Finnish (FIN) AF: 0.234 AC: 8830 AN: 37712

Middle Eastern (MID) AF: 0.146 AC: 580 AN: 3962

European-Non Finnish (NFE) AF: 0.141 AC: 134564 AN: 952270

Other (OTH) AF: 0.125 AC: 6685 AN: 53324

GnomAD4 genome AF: 0.114 AC: 17388 AN: 152122 Hom.: 1228 Cov.: 32 AF XY: 0.118 AC XY: 8757 AN XY: 74368

African (AFR) AF: 0.0580 AC: 2409 AN: 41510

American (AMR) AF: 0.0972 AC: 1486 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3466

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5174

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2636 AN: 10566

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9554 AN: 67974

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.134 Hom.: 2601

Bravo AF: 0.102

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.80
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		0.52
PromoterAI		-0.082	Neutral
Mutation Taster		=300/0	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: rs3213460; hg19: chr11-102668882; COSMIC: COSV59511175;