21-45123464-T-G

Position:

• chr21-45123464-T-G

Variant summary

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

The NM_001112.4(ADARB1):​c.-219-4938T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,158 control chromosomes in the GnomAD database, including 56,489 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 0.86 (56489 hom., cov: 32)
• Consequence: ADARB1 NM_001112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB1	NM_001112.4	c.-219-4938T>G		intron_variant		ENST00000348831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB1	ENST00000348831.9	c.-219-4938T>G		intron_variant		1	NM_001112.4	P1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130815 AN: 152040 Hom.: 56477 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.860 AC: 130878 AN: 152158 Hom.: 56489 Cov.: 32 AF XY: 0.860 AC XY: 63964 AN XY: 74396

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.879

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.861

Alfa AF: 0.879 Hom.: 2889

Bravo AF: 0.853

Asia WGS AF: 0.879 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.81

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: rs391834; hg19: chr21-46543379;