dbSNP rs9983925: ADARB1:c.1748-3907C>T (chr21-45216929-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001112.4(ADARB1):c.1748-3907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,378 control chromosomes in the GnomAD database, including 18,182 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 0.45 ( 18182 hom., cov: 30)

Consequence

ADARB1
NM_001112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.545

Publications

8 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=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADARB1	NM_001112.4	MANE Select	c.1748-3907C>T	intron	N/A	NP_001103.1	P78563-2
ADARB1	NM_001410722.1		c.1895-3907C>T	intron	N/A	NP_001397651.1	A0A994J7T5
ADARB1	NM_015833.4		c.1868-3907C>T	intron	N/A	NP_056648.1	P78563-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADARB1	ENST00000348831.9	TSL:1 MANE Select	c.1748-3907C>T	intron	N/A	ENSP00000015877.6	P78563-2
ADARB1	ENST00000360697.4	TSL:1	c.1868-3907C>T	intron	N/A	ENSP00000353920.3	P78563-1
ADARB1	ENST00000389863.8	TSL:1	c.1868-3907C>T	intron	N/A	ENSP00000374513.4	P78563-3

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68179

AN:

151260

Hom.:

18147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.451

AC:

68256

AN:

151378

Hom.:

18182

Cov.:

AF XY:

0.448

AC XY:

33154

AN XY:

73934

show subpopulations

African (AFR)

AF:

0.751

AC:

31052

AN:

41358

American (AMR)

AF:

0.395

AC:

6012

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1174

AN:

3464

East Asian (EAS)

AF:

0.524

AC:

2679

AN:

5114

South Asian (SAS)

AF:

0.264

AC:

1269

AN:

4798

European-Finnish (FIN)

AF:

0.372

AC:

3867

AN:

10394

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.309

AC:

20945

AN:

67710

Other (OTH)

AF:

0.422

AC:

887

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1613

3226

4838

6451

8064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.338

Hom.:

10801

Bravo

AF:

0.468

Asia WGS

AF:

0.376

AC:

1301

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.6

(source)

DANN

Benign

0.40

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over