rs9983925

Positions:

• chr21-45216929-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ADARB1	NM_001112.4	c.1748-3907C>T		intron_variant		ENST00000348831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB1	ENST00000348831.9	c.1748-3907C>T		intron_variant		1	NM_001112.4	P1

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

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.422

Alfa AF: 0.335 Hom.: 8906

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

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

Other links and lift over

dbSNP: rs9983925; hg19: chr21-46636844;