rs2838815

Variant names:

• chr21-45209675-C-T
• rs2838815
• NM_001112.4:c.1747+4939C>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.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
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	NM_001112.4	MANE Select	c.1747+4939C>T		intron	N/A	NP_001103.1	P78563-2
	ADARB1	NM_001410722.1		c.1894+4939C>T		intron	N/A	NP_001397651.1	A0A994J7T5
	ADARB1	NM_015833.4		c.1867+4939C>T		intron	N/A	NP_056648.1	P78563-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	ENST00000348831.9	TSL:1 MANE Select	c.1747+4939C>T		intron	N/A	ENSP00000015877.6	P78563-2
	ADARB1	ENST00000360697.4	TSL:1	c.1867+4939C>T		intron	N/A	ENSP00000353920.3	P78563-1
	ADARB1	ENST00000389863.8	TSL:1	c.1867+4939C>T		intron	N/A	ENSP00000374513.4	P78563-3

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

African (AFR) AF: 0.443 AC: 18353 AN: 41442

American (AMR) AF: 0.447 AC: 6827 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2538 AN: 5154

South Asian (SAS) AF: 0.571 AC: 2750 AN: 4816

European-Finnish (FIN) AF: 0.608 AC: 6414 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37539 AN: 67936

Other (OTH) AF: 0.496 AC: 1049 AN: 2114

Alfa AF: 0.529 Hom.: 75305

Bravo AF: 0.496

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		0.080
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: rs2838815; hg19: chr21-46629590;