Variant chr2-9521055-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003183.6(ADAM17):c.957+148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 463,832 control chromosomes in the GnomAD database, including 87,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31406 hom., cov: 26)

Exomes 𝑓: 0.57 ( 55994 hom. )

Consequence

ADAM17
NM_003183.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.670

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:

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=-0.92).

BP6

Variant 2-9521055-T-C is Benign according to our data. Variant chr2-9521055-T-C is described in ClinVar as [Benign]. Clinvar id is 1263774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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.957+148A>G		intron_variant		ENST00000310823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM17	ENST00000310823.8 linkuse as main transcript	c.957+148A>G		intron_variant		1	NM_003183.6	P1	P78536-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

94546

AN:

149540

Hom.:

31375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

0.850

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.0905

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.752

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.565

AC:

177634

AN:

314174

Hom.:

55994

AF XY:

0.564

AC XY:

95142

AN XY:

168636

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.668

Gnomad4 EAS exome

AF:

0.0484

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.531

Gnomad4 NFE exome

AF:

0.656

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.632

AC:

94621

AN:

149658

Hom.:

31406

Cov.:

AF XY:

0.616

AC XY:

44899

AN XY:

72908

show subpopulations

Gnomad4 AFR

AF:

0.718

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.0901

Gnomad4 SAS

AF:

0.443

Gnomad4 FIN

AF:

0.520

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.653

Alfa

AF:

0.672

Hom.:

4316

Bravo

AF:

0.634

Asia WGS

AF:

0.316

AC:

1102

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.45

DANN

Benign

0.31

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