dbSNP rs4819035: ADARB1:n.*1634T>G (chr21-45225800-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000389861.7(ADARB1):n.*1634T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 388,702 control chromosomes in the GnomAD database, including 11,387 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3704 hom., cov: 32)

Exomes 𝑓: 0.25 ( 7683 hom. )

Consequence

ADARB1
ENST00000389861.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.179

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia, microcephaly, and seizures
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ADARB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4 link	c.*3603T>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000348831.9	NP_001103.1	P78563-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB1	ENST00000348831.9 link	c.*3603T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001112.4	ENSP00000015877.6		P78563-2

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30469

AN:

152100

Hom.:

3702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.250

AC:

59193

AN:

236484

Hom.:

7683

Cov.:

AF XY:

0.252

AC XY:

30286

AN XY:

119968

show subpopulations

African (AFR)

AF:

0.0655

AC:

455

AN:

6950

American (AMR)

AF:

0.169

AC:

1202

AN:

7098

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

2044

AN:

8852

East Asian (EAS)

AF:

0.200

AC:

4433

AN:

22112

South Asian (SAS)

AF:

0.281

AC:

597

AN:

2122

European-Finnish (FIN)

AF:

0.235

AC:

4638

AN:

19736

Middle Eastern (MID)

AF:

0.296

AC:

373

AN:

1260

European-Non Finnish (NFE)

AF:

0.274

AC:

41834

AN:

152666

Other (OTH)

AF:

0.231

AC:

3617

AN:

15688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2033

4066

6098

8131

10164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.200

AC:

30472

AN:

152218

Hom.:

3704

Cov.:

AF XY:

0.202

AC XY:

15037

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0639

AC:

2657

AN:

41562

American (AMR)

AF:

0.193

AC:

2957

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

784

AN:

3470

East Asian (EAS)

AF:

0.161

AC:

837

AN:

5188

South Asian (SAS)

AF:

0.281

AC:

1354

AN:

4826

European-Finnish (FIN)

AF:

0.242

AC:

2562

AN:

10594

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18596

AN:

67980

Other (OTH)

AF:

0.201

AC:

423

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1201

2401

3602

4802

6003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

6404

Bravo

AF:

0.190

Asia WGS

AF:

0.184

AC:

641

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

(source)

DANN

Benign

0.49

PhyloP100

-0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over