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. The variant received -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
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	NM_001112.4	MANE Select	c.-220+26750A>G		intron	N/A	NP_001103.1
	ADARB1	NM_015833.4		c.-220+26750A>G		intron	N/A	NP_056648.1
	ADARB1	NM_015834.4		c.-220+26750A>G		intron	N/A	NP_056649.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB1	ENST00000348831.9	TSL:1 MANE Select	c.-220+26750A>G		intron	N/A	ENSP00000015877.6
	ADARB1	ENST00000437626.5	TSL:1	c.-220+26750A>G		intron	N/A	ENSP00000414600.2
	ADARB1	ENST00000389863.8	TSL:1	c.-220+26750A>G		intron	N/A	ENSP00000374513.4

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

African (AFR) AF: 0.200 AC: 8301 AN: 41536

American (AMR) AF: 0.195 AC: 2984 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3468

East Asian (EAS) AF: 0.155 AC: 803 AN: 5182

South Asian (SAS) AF: 0.0729 AC: 352 AN: 4826

European-Finnish (FIN) AF: 0.156 AC: 1657 AN: 10602

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8546 AN: 67996

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.148 Hom.: 600

Bravo AF: 0.163

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17004734; hg19: chr21-46521458;