Variant chr2-9490115-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003183.6(ADAM17):c.*61delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20928 hom., cov: 0)

Exomes 𝑓: 0.56 ( 203790 hom. )

Consequence

ADAM17
NM_003183.6 3_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.00

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:

IAH1 (HGNC:27696): (isoamyl acetate hydrolyzing esterase 1 (putative)) Enables identical protein binding activity. Predicted to be involved in lipid catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

IAH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-9490115-AT-A is Benign according to our data. Variant chr2-9490115-AT-A is described in ClinVar as [Benign]. Clinvar id is 1188896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM17	NM_003183.6 link	c.*61delA		3_prime_UTR_variant	19/19	ENST00000310823.8	NP_003174.3	P78536-1B2RNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM17	ENST00000310823 link	c.*61delA		3_prime_UTR_variant	19/19	1	NM_003183.6	ENSP00000309968.3		P78536-1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

77991

AN:

151428

Hom.:

20911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.0912

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.556

AC:

707020

AN:

1271914

Hom.:

203790

Cov.:

AF XY:

0.555

AC XY:

346864

AN XY:

624660

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.630

Gnomad4 EAS exome

AF:

0.0624

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.594

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.515

AC:

78045

AN:

151544

Hom.:

20928

Cov.:

AF XY:

0.503

AC XY:

37286

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.0908

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.593

Gnomad4 OTH

AF:

0.556

Alfa

AF:

0.554

Hom.:

2195

Bravo

AF:

0.506

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 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. 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

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