rs2071232

Positions:

• chr11-102794938-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.899+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,246 control chromosomes in the GnomAD database, including 3,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3200 hom., cov: 32)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190

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 11-102794938-T-C is Benign according to our data. Variant chr11-102794938-T-C is described in ClinVar as [Benign]. Clinvar id is 1234842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP1	NM_002421.4	c.899+236A>G		intron_variant		ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1	n.507-210T>C		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.701+236A>G		intron_variant			NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.899+236A>G		intron_variant		1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7	n.325-3086T>C		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6	n.507-210T>C		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1	n.345-3086T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29426 AN: 152128 Hom.: 3181 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.194 AC: 29472 AN: 152246 Hom.: 3200 Cov.: 32 AF XY: 0.197 AC XY: 14631 AN XY: 74442

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.185

Alfa AF: 0.197 Hom.: 1662

Bravo AF: 0.195

Asia WGS AF: 0.288 AC: 1003 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.52

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: rs2071232; hg19: chr11-102665669;