rs7945189

Positions:

• chr11-102789833-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_038390.1(WTAPP1):​n.390-3312C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 151,300 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (500 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WTAPP1 NR_038390.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

Genes affected

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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
WTAPP1	NR_038390.1	n.390-3312C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WTAPP1	ENST00000371455.7	n.325-8191C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11194 AN: 151182 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0740 AC: 11197 AN: 151300 Hom.: 500 Cov.: 32 AF XY: 0.0735 AC XY: 5430 AN XY: 73866

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.0590

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0955 Hom.: 967

Bravo AF: 0.0684

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7945189; hg19: chr11-102660564;