rs17004734

Variant names:

• chr21-45101543-A-G
• rs17004734
• NM_001112.4:c.-220+26750A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-45101543-A-G
• chr21-45101543-A-T

Variant summary

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

The NM_001112.4(ADARB1):​c.-220+26750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,228 control chromosomes in the GnomAD database, including 1,940 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 0.16 (1940 hom., cov: 33)
• Consequence: ADARB1 NM_001112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4	c.-220+26750A>G		intron_variant	Intron 1 of 10	ENST00000348831.9	NP_001103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB1	ENST00000348831.9	c.-220+26750A>G		intron_variant	Intron 1 of 10	1	NM_001112.4	ENSP00000015877.6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23767 AN: 152110 Hom.: 1938 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.156 AC: 23797 AN: 152228 Hom.: 1940 Cov.: 33 AF XY: 0.155 AC XY: 11539 AN XY: 74426

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.160

Alfa AF: 0.144 Hom.: 512

Bravo AF: 0.163

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17004734; hg19: chr21-46521458;