21-45123464-T-G

Variant names:

• chr21-45123464-T-G
• rs391834
• NM_001112.4:c.-219-4938T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 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.-219-4938T>G		intron	N/A	NP_001103.1	P78563-2
	ADARB1	NM_015833.4		c.-219-4938T>G		intron	N/A	NP_056648.1	P78563-1
	ADARB1	NM_015834.4		c.-219-4938T>G		intron	N/A	NP_056649.1	P78563-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	ENST00000348831.9	TSL:1 MANE Select	c.-219-4938T>G		intron	N/A	ENSP00000015877.6	P78563-2
	ADARB1	ENST00000389863.8	TSL:1	c.-219-4938T>G		intron	N/A	ENSP00000374513.4	P78563-3
	ADARB1	ENST00000389861.7	TSL:1	n.-337-4938T>G		intron	N/A	ENSP00000516121.1	P78563-2

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

African (AFR) AF: 0.799 AC: 33155 AN: 41486

American (AMR) AF: 0.830 AC: 12677 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2890 AN: 3466

East Asian (EAS) AF: 0.824 AC: 4261 AN: 5172

South Asian (SAS) AF: 0.879 AC: 4238 AN: 4824

European-Finnish (FIN) AF: 0.896 AC: 9494 AN: 10598

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61253 AN: 68014

Other (OTH) AF: 0.861 AC: 1817 AN: 2110

Alfa AF: 0.873 Hom.: 3149

Bravo AF: 0.853

Asia WGS AF: 0.879 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.81
PhyloP100		-1.2
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: rs391834; hg19: chr21-46543379;