rs2239008

chr11-102790349-G-Achr11-102790349-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):c.*63C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 938,944 control chromosomes in the GnomAD database, including 22,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3180 hom., cov: 33)
  • Exomes 𝑓: 0.21 (18838 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840

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:44115): (WTAP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-102790349-G-A is Benign according to our data. Variant chr11-102790349-G-A is described in ClinVar as [Benign]. Clinvar id is 1233849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.*63C>T		3_prime_UTR_variant	10/10	ENST00000315274.7
WTAPP1	NR_038390.1	n.390-2796G>A		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.*63C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.*63C>T		3_prime_UTR_variant	10/10	1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-7675G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29255 AN: 152012 Hom.: 3162 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.211 AC: 166113 AN: 786814 Hom.: 18838 Cov.: 10 AF XY: 0.210 AC XY: 86254 AN XY: 409922

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.193 AC: 29292 AN: 152130 Hom.: 3180 Cov.: 33 AF XY: 0.196 AC XY: 14544 AN XY: 74360

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.185

Alfa AF: 0.193 Hom.: 1018

Bravo AF: 0.194

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239008; hg19: chr11-102661080; COSMIC: COSV59509723;