NM_001112.4:c.*3603T>G

Variant names:

• chr21-45225800-T-G
• rs4819035
• NM_001112.4:c.*3603T>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.*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
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 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.*3603T>G		3_prime_UTR	Exon 11 of 11	NP_001103.1	P78563-2
	ADARB1	NM_001410722.1		c.*3603T>G		3_prime_UTR	Exon 10 of 10	NP_001397651.1	A0A994J7T5
	ADARB1	NM_015833.4		c.*3603T>G		3_prime_UTR	Exon 12 of 12	NP_056648.1	P78563-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	ENST00000348831.9	TSL:1 MANE Select	c.*3603T>G		3_prime_UTR	Exon 11 of 11	ENSP00000015877.6	P78563-2
	ADARB1	ENST00000360697.4	TSL:1	c.*3603T>G		3_prime_UTR	Exon 10 of 10	ENSP00000353920.3	P78563-1
	ADARB1	ENST00000389863.8	TSL:1	c.*245T>G		3_prime_UTR	Exon 13 of 13	ENSP00000374513.4	P78563-3

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

African (AFR) AF: 0.0655 AC: 455 AN: 6950

American (AMR) AF: 0.169 AC: 1202 AN: 7098

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 2044 AN: 8852

East Asian (EAS) AF: 0.200 AC: 4433 AN: 22112

South Asian (SAS) AF: 0.281 AC: 597 AN: 2122

European-Finnish (FIN) AF: 0.235 AC: 4638 AN: 19736

Middle Eastern (MID) AF: 0.296 AC: 373 AN: 1260

European-Non Finnish (NFE) AF: 0.274 AC: 41834 AN: 152666

Other (OTH) AF: 0.231 AC: 3617 AN: 15688

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

African (AFR) AF: 0.0639 AC: 2657 AN: 41562

American (AMR) AF: 0.193 AC: 2957 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3470

East Asian (EAS) AF: 0.161 AC: 837 AN: 5188

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4826

European-Finnish (FIN) AF: 0.242 AC: 2562 AN: 10594

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18596 AN: 67980

Other (OTH) AF: 0.201 AC: 423 AN: 2106

Alfa AF: 0.243 Hom.: 6404

Bravo AF: 0.190

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4819035; hg19: chr21-46645715;