rs34367192

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003183.6(ADAM17):c.1545-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,310,460 control chromosomes in the GnomAD database, including 151,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14253 hom., cov: 31)

Exomes 𝑓: 0.47 ( 136771 hom. )

Consequence

ADAM17
NM_003183.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.44

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]

ADAM17 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 2-9502349-C-T is Benign according to our data. Variant chr2-9502349-C-T is described in ClinVar as [Benign]. Clinvar id is 1188944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM17	NM_003183.6 linkuse as main transcript	c.1545-73G>A		intron_variant		ENST00000310823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM17	ENST00000310823.8 linkuse as main transcript	c.1545-73G>A		intron_variant		1	NM_003183.6	P1	P78536-1
	ENST00000472619.2 linkuse as main transcript	n.76+808C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63080

AN:

151742

Hom.:

14257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.0303

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.468

GnomAD4 exome

AF:

0.473

AC:

547772

AN:

1158600

Hom.:

136771

AF XY:

0.472

AC XY:

277357

AN XY:

587216

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.0232

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.456

Gnomad4 NFE exome

AF:

0.516

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.416

AC:

63106

AN:

151860

Hom.:

14253

Cov.:

AF XY:

0.407

AC XY:

30232

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.0302

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.514

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.450

Hom.:

2795

Bravo

AF:

0.403

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Inflammatory skin and bowel disease, neonatal, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

Cadd

Benign

0.0090

Dann

Benign

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over