rs4819035

Variant names:

• chr21-45225800-T-G
• rs4819035
• NM_001112.4:c.*3603T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001112.4(ADARB1):​c.*3603T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 388,702 control chromosomes in the GnomAD database, including 11,387 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 0.20 (3704 hom., cov: 32)
  • Exomes 𝑓: 0.25 (7683 hom.)
• Consequence: ADARB1 NM_001112.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4	c.*3603T>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000348831.9	NP_001103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB1	ENST00000348831.9	c.*3603T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001112.4	ENSP00000015877.6

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30469 AN: 152100 Hom.: 3702 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.250 AC: 59193 AN: 236484 Hom.: 7683 Cov.: 3 AF XY: 0.252 AC XY: 30286 AN XY: 119968

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.200 AC: 30472 AN: 152218 Hom.: 3704 Cov.: 32 AF XY: 0.202 AC XY: 15037 AN XY: 74428

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.201

Alfa AF: 0.252 Hom.: 5184

Bravo AF: 0.190

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4819035; hg19: chr21-46645715;