11-102789366-G-A

Position:

• chr11-102789366-G-A

Variant summary

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

The ENST00000525739.6(WTAPP1):​n.390-3779G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,194 control chromosomes in the GnomAD database, including 1,156 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 0.11 (1156 hom., cov: 32)
• Consequence: WTAPP1 ENST00000525739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.81).
• 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	Protein	UniProt
WTAPP1	NR_038390.1	n.390-3779G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WTAPP1	ENST00000371455.7	n.325-8658G>A		intron_variant		4
WTAPP1	ENST00000525739.6	n.390-3779G>A		intron_variant		2
WTAPP1	ENST00000544704.1	n.344+5302G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16255 AN: 152076 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0671

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: 0.107 AC: 16252 AN: 152194 Hom.: 1156 Cov.: 32 AF XY: 0.110 AC XY: 8214 AN XY: 74396

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.122

Alfa AF: 0.113 Hom.: 175

Bravo AF: 0.0945

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11600510; hg19: chr11-102660097;