Variant 21-45134743-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001112.4(ADARB1):c.-48+6170C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 530,664 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 3 hom. )

Consequence

ADARB1
NM_001112.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370

Variant links:

Genes affected

ADARB1 (HGNC:226): (adenosine deaminase RNA specific B1) This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region. [provided by RefSeq, Jul 2008]

ADARB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 21-45134743-C-G is Benign according to our data. Variant chr21-45134743-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652783.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00324 (491/151718) while in subpopulation AMR AF= 0.0113 (173/15282). AF 95% confidence interval is 0.00994. There are 4 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB1	NM_001112.4 linkuse as main transcript	c.-48+6170C>G		intron_variant		ENST00000348831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB1	ENST00000348831.9 linkuse as main transcript	c.-48+6170C>G		intron_variant		1	NM_001112.4	P1	P78563-2

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

492

AN:

151600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00310

AC:

753

AN:

242988

Hom.:

AF XY:

0.00315

AC XY:

416

AN XY:

131968

show subpopulations

Gnomad AFR exome

AF:

0.000874

Gnomad AMR exome

AF:

0.00703

Gnomad ASJ exome

AF:

0.00515

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.000602

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00358

Gnomad OTH exome

AF:

0.00624

GnomAD4 exome

AF:

0.00298

AC:

1129

AN:

378946

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

624

AN XY:

215730

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00740

Gnomad4 ASJ exome

AF:

0.00489

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000817

Gnomad4 FIN exome

AF:

0.0000949

Gnomad4 NFE exome

AF:

0.00329

Gnomad4 OTH exome

AF:

0.00314

GnomAD4 genome

AF:

0.00324

AC:

491

AN:

151718

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

252

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.00138

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00328

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00379

Asia WGS

AF:

0.00433

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ADARB1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

DANN

Benign

0.70

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