rs17878931

chr11-102795924-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.626-317C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,098 control chromosomes in the GnomAD database, including 1,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1144 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18

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=-0.9).
• BP6: Variant 11-102795924-G-T is Benign according to our data. Variant chr11-102795924-G-T is described in ClinVar as [Benign]. Clinvar id is 1224129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.626-317C>A		intron_variant		ENST00000315274.7
WTAPP1	NR_038390.1	n.583+700G>T		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.428-317C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.626-317C>A		intron_variant		1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-2100G>T		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6	n.583+700G>T		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1	n.345-2100G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16158 AN: 151980 Hom.: 1143 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.106 AC: 16151 AN: 152098 Hom.: 1144 Cov.: 33 AF XY: 0.110 AC XY: 8179 AN XY: 74350

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.0660

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.122

Alfa AF: 0.114 Hom.: 142

Bravo AF: 0.0939

Asia WGS AF: 0.0450 AC: 157 AN: 3476

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	-0.90
Cadd	Benign	0.0060
Dann	Benign	0.46

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: rs17878931; hg19: chr11-102666655;