NM_001112.4:c.1748-6605T>C

Variant names:

• chr21-45214231-T-C
• rs2225434
• NM_001112.4:c.1748-6605T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001112.4(ADARB1):​c.1748-6605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,992 control chromosomes in the GnomAD database, including 20,837 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 0.52 (20837 hom., cov: 32)
• Consequence: ADARB1 NM_001112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB1	NM_001112.4	c.1748-6605T>C		intron_variant	Intron 9 of 10	ENST00000348831.9	NP_001103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB1	ENST00000348831.9	c.1748-6605T>C		intron_variant	Intron 9 of 10	1	NM_001112.4	ENSP00000015877.6

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78890 AN: 151872 Hom.: 20841 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.519 AC: 78909 AN: 151992 Hom.: 20837 Cov.: 32 AF XY: 0.523 AC XY: 38823 AN XY: 74282

African (AFR) AF: 0.448 AC: 18560 AN: 41444

American (AMR) AF: 0.449 AC: 6855 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1692 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2562 AN: 5176

South Asian (SAS) AF: 0.579 AC: 2785 AN: 4812

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10540

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38201 AN: 67960

Other (OTH) AF: 0.502 AC: 1060 AN: 2112

Alfa AF: 0.520 Hom.: 2982

Bravo AF: 0.503

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		0.74
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: rs2225434; hg19: chr21-46634146; COSMIC: COSV62347535;