11-102791026-G-A

Position:

• chr11-102791026-G-A

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.1197-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,268 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (499 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32

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=-0.91).
• BP6: Variant 11-102791026-G-A is Benign according to our data. Variant chr11-102791026-G-A is described in ClinVar as [Benign]. Clinvar id is 1260475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.1197-220C>T		intron_variant		ENST00000315274.7
WTAPP1	NR_038390.1	n.390-2119G>A		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.999-220C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.1197-220C>T		intron_variant		1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-6998G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11170 AN: 152150 Hom.: 497 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0734 AC: 11172 AN: 152268 Hom.: 499 Cov.: 33 AF XY: 0.0730 AC XY: 5434 AN XY: 74454

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0571 Hom.: 83

Bravo AF: 0.0683

Asia WGS AF: 0.0960 AC: 335 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.49

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: rs17878905; hg19: chr11-102661757;