rs2838815

chr21-45209675-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.1747+4939C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,964 control chromosomes in the GnomAD database, including 20,252 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 0.51 (20252 hom., cov: 32)
• Consequence: ADARB1 NM_001112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB1	NM_001112.4	c.1747+4939C>T		intron_variant		ENST00000348831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB1	ENST00000348831.9	c.1747+4939C>T		intron_variant		1	NM_001112.4	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77766 AN: 151846 Hom.: 20256 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.512 AC: 77784 AN: 151964 Hom.: 20252 Cov.: 32 AF XY: 0.516 AC XY: 38298 AN XY: 74282

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.496

Alfa AF: 0.537 Hom.: 49288

Bravo AF: 0.496

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.2
Dann	Benign	0.48

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: rs2838815; hg19: chr21-46629590;