rs17881293

Positions:

• chr11-102791735-T-C

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.1034-240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,262 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.083 (694 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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=-0.85).
• BP6: Variant 11-102791735-T-C is Benign according to our data. Variant chr11-102791735-T-C is described in ClinVar as [Benign]. Clinvar id is 1273339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP1	NM_002421.4	c.1034-240A>G		intron_variant		ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1	n.390-1410T>C		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.836-240A>G		intron_variant			NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.1034-240A>G		intron_variant		1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7	n.325-6289T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12651 AN: 152144 Hom.: 694 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0831 AC: 12659 AN: 152262 Hom.: 694 Cov.: 33 AF XY: 0.0806 AC XY: 6005 AN XY: 74458

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0719

Alfa AF: 0.0761 Hom.: 103

Bravo AF: 0.0848

Asia WGS AF: 0.0340 AC: 118 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.67

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: rs17881293; hg19: chr11-102662466;