chr11-102790864-A-G

Position:

• chr11-102790864-A-G

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.1197-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 917,102 control chromosomes in the GnomAD database, including 54,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8909 hom., cov: 32)
  • Exomes 𝑓: 0.34 (45822 hom.)
• Consequence: MMP1 ENST00000315274.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0980

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=-0.82).
• BP6: Variant 11-102790864-A-G is Benign according to our data. Variant chr11-102790864-A-G is described in ClinVar as [Benign]. Clinvar id is 1182135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP1	NM_002421.4	c.1197-58T>C		intron_variant		ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1	n.390-2281A>G		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.999-58T>C		intron_variant			NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.1197-58T>C		intron_variant		1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7	n.325-7160A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51034 AN: 151884 Hom.: 8905 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.341 AC: 260858 AN: 765100 Hom.: 45822 AF XY: 0.341 AC XY: 137924 AN XY: 404608

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.336 AC: 51065 AN: 152002 Hom.: 8909 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74324

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.321

Alfa AF: 0.351 Hom.: 14284

Bravo AF: 0.332

Asia WGS AF: 0.231 AC: 803 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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.75

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: rs470747; hg19: chr11-102661595;