Variant 20-3669610-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_025220.5(ADAM33):c.2268C>T(p.His756=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,603,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

ADAM33
NM_025220.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) 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 biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ADAM33 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 20-3669610-G-A is Benign according to our data. Variant chr20-3669610-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 729623.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.179 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.2268C>T	p.His756=	synonymous_variant	20/22	ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7 linkuse as main transcript	c.2268C>T	p.His756=	synonymous_variant	20/22	1	NM_025220.5	P4	Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000515

AC:

117

AN:

227364

Hom.:

AF XY:

0.000547

AC XY:

AN XY:

122436

show subpopulations

Gnomad AFR exome

AF:

0.000281

Gnomad AMR exome

AF:

0.000688

Gnomad ASJ exome

AF:

0.000321

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000732

Gnomad FIN exome

AF:

0.0000526

Gnomad NFE exome

AF:

0.000641

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000622

AC:

903

AN:

1450822

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

460

AN XY:

720316

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000701

Gnomad4 ASJ exome

AF:

0.000350

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000791

Gnomad4 FIN exome

AF:

0.0000762

Gnomad4 NFE exome

AF:

0.000672

Gnomad4 OTH exome

AF:

0.000667

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152234

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000679

Hom.:

Bravo

AF:

0.000646

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.47

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