rs5031036

Positions:

• chr11-102795433-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000315274.7(MMP1):​c.781+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,610,094 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (773 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3270 hom.)
• Consequence: MMP1 ENST00000315274.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.468

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-102795433-T-C is Benign according to our data. Variant chr11-102795433-T-C is described in ClinVar as [Benign]. Clinvar id is 1288920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP1	NM_002421.4	c.781+19A>G		intron_variant		ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1	n.583+209T>C		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.583+19A>G		intron_variant			NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.781+19A>G		intron_variant		1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7	n.325-2591T>C		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6	n.583+209T>C		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1	n.345-2591T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 13090 AN: 152098 Hom.: 773 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0736

GnomAD3 exomes AF: 0.0577 AC: 14266 AN: 247070 Hom.: 534 AF XY: 0.0556 AC XY: 7418 AN XY: 133470

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0432

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.0107

Gnomad SAS exome AF: 0.0349

Gnomad FIN exome AF: 0.0744

Gnomad NFE exome AF: 0.0595

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0622 AC: 90725 AN: 1457878 Hom.: 3270 Cov.: 34 AF XY: 0.0611 AC XY: 44275 AN XY: 725030

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.00857

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.0641

Gnomad4 OTH exome AF: 0.0595

GnomAD4 genome AF: 0.0861 AC: 13103 AN: 152216 Hom.: 773 Cov.: 32 AF XY: 0.0833 AC XY: 6204 AN XY: 74444

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0727 Hom.: 112

Bravo AF: 0.0876

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.81
CADD	Benign	1.2
DANN	Benign	0.39

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: rs5031036; hg19: chr11-102666164;