rs9983925

Variant names:

• chr21-45216929-C-T
• rs9983925
• NM_001112.4:c.1748-3907C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 8 publications found

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4	c.1748-3907C>T		intron_variant	Intron 9 of 10	ENST00000348831.9	NP_001103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB1	ENST00000348831.9	c.1748-3907C>T		intron_variant	Intron 9 of 10	1	NM_001112.4	ENSP00000015877.6

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68179 AN: 151260 Hom.: 18147 Cov.: 30

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.: 30 AF XY: 0.448 AC XY: 33154 AN XY: 73934

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.40
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9983925; hg19: chr21-46636844;