rs470358

Positions:

• chr11-102797971-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.105+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,545,902 control chromosomes in the GnomAD database, including 288,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33408 hom., cov: 32)
  • Exomes 𝑓: 0.60 (255473 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

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=-0.82).
• BP6: Variant 11-102797971-T-C is Benign according to our data. Variant chr11-102797971-T-C is described in ClinVar as [Benign]. Clinvar id is 1235418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.105+17A>G		intron_variant		ENST00000315274.7
WTAPP1	NR_038390.1	n.584-53T>C		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.-53+128A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.105+17A>G		intron_variant		1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-53T>C		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6	n.584-53T>C		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1	n.345-53T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99685 AN: 151992 Hom.: 33379 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.602 AC: 145180 AN: 240986 Hom.: 44336 AF XY: 0.599 AC XY: 78087 AN XY: 130290

Gnomad AFR exome AF: 0.812

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.650

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.570

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.603 AC: 840613 AN: 1393792 Hom.: 255473 Cov.: 21 AF XY: 0.602 AC XY: 419120 AN XY: 696696

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.611

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.656 AC: 99766 AN: 152110 Hom.: 33408 Cov.: 32 AF XY: 0.652 AC XY: 48509 AN XY: 74358

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.639

Alfa AF: 0.612 Hom.: 28862

Bravo AF: 0.661

Asia WGS AF: 0.633 AC: 2200 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	-0.82
CADD	Benign	2.0
DANN	Benign	0.62

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: rs470358; hg19: chr11-102668702; COSMIC: COSV59510658;