rs2838816

Variant names:

• chr21-45210127-G-A
• rs2838816
• NM_001112.4:c.1747+5391G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-45210127-G-A
• chr21-45210127-G-C

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+5391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,146 control chromosomes in the GnomAD database, including 2,354 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 0.15 (2354 hom., cov: 33)
• Consequence: ADARB1 NM_001112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4	c.1747+5391G>A		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.1747+5391G>A		intron_variant	Intron 9 of 10	1	NM_001112.4	ENSP00000015877.6

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22725 AN: 152028 Hom.: 2345 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.150 AC: 22787 AN: 152146 Hom.: 2354 Cov.: 33 AF XY: 0.149 AC XY: 11052 AN XY: 74404

African (AFR) AF: 0.288 AC: 11939 AN: 41458

American (AMR) AF: 0.165 AC: 2516 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3472

East Asian (EAS) AF: 0.152 AC: 785 AN: 5180

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4826

European-Finnish (FIN) AF: 0.0775 AC: 821 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5441 AN: 67994

Other (OTH) AF: 0.154 AC: 326 AN: 2116

Alfa AF: 0.110 Hom.: 3870

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		-0.24
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: rs2838816; hg19: chr21-46630042;