rs1880439

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003183.6(ADAM17):​c.230+1485G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,244 control chromosomes in the GnomAD database, including 1,643 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 0.14 ( 1643 hom., cov: 33)

Consequence

ADAM17
NM_003183.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295
Variant links:
Genes affected
ADAM17 (HGNC:195): (ADAM metallopeptidase domain 17) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands, and plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. Additionally, this protease may play a role in viral infection through its cleavage of ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAM17NM_003183.6 linkuse as main transcriptc.230+1485G>T intron_variant ENST00000310823.8
ADAM17NM_001382777.1 linkuse as main transcriptc.-451+1485G>T intron_variant
ADAM17NM_001382778.1 linkuse as main transcriptc.-693+1485G>T intron_variant
ADAM17XM_047445610.1 linkuse as main transcriptc.137+1485G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAM17ENST00000310823.8 linkuse as main transcriptc.230+1485G>T intron_variant 1 NM_003183.6 P1P78536-1

Frequencies

GnomAD3 genomes
AF:
0.143
AC:
21732
AN:
152126
Hom.:
1641
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.150
Gnomad AMI
AF:
0.169
Gnomad AMR
AF:
0.111
Gnomad ASJ
AF:
0.141
Gnomad EAS
AF:
0.0610
Gnomad SAS
AF:
0.105
Gnomad FIN
AF:
0.0913
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.138
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.143
AC:
21742
AN:
152244
Hom.:
1643
Cov.:
33
AF XY:
0.138
AC XY:
10285
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.150
Gnomad4 AMR
AF:
0.110
Gnomad4 ASJ
AF:
0.141
Gnomad4 EAS
AF:
0.0607
Gnomad4 SAS
AF:
0.106
Gnomad4 FIN
AF:
0.0913
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.137
Alfa
AF:
0.156
Hom.:
1898
Bravo
AF:
0.144
Asia WGS
AF:
0.0920
AC:
321
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.81
DANN
Benign
0.38

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1880439; hg19: chr2-9681797; API