rs2271275

Variant names:

• chr10-1185028-C-T
• rs2271275
• NM_018702.4:c.1876G>A

Variant summary

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

The NM_018702.4(ADARB2):​c.1876G>A​(p.Ala626Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,611,578 control chromosomes in the GnomAD database, including 353,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (25933 hom., cov: 35)
  • Exomes 𝑓: 0.67 (328042 hom.)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 29 publications found

Genes affected

ADARB2 (HGNC:227): (adenosine deaminase RNA specific B2 (inactive)) This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008]

LINC00200 (HGNC:30974): (long intergenic non-protein coding RNA 200)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.927142E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018702.4. 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
	ADARB2	NM_018702.4	MANE Select	c.1876G>A	p.Ala626Thr	missense	Exon 9 of 10	NP_061172.1	Q9NS39-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB2	ENST00000381312.6	TSL:1 MANE Select	c.1876G>A	p.Ala626Thr	missense	Exon 9 of 10	ENSP00000370713.1	Q9NS39-1
	ADARB2	ENST00000381310.7	TSL:1	c.403G>A	p.Ala135Thr	missense	Exon 2 of 3	ENSP00000370711.3	Q9NS39-2
	ADARB2	ENST00000474762.5	TSL:1	n.76G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85498 AN: 152078 Hom.: 25930 Cov.: 35

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.618

GnomAD2 exomes AF: 0.639 AC: 157758 AN: 246950 AF XY: 0.650

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.720

Gnomad EAS exome AF: 0.675

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.684

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.667 AC: 974089 AN: 1459380 Hom.: 328042 Cov.: 69 AF XY: 0.670 AC XY: 486227 AN XY: 725906

African (AFR) AF: 0.300 AC: 10018 AN: 33432

American (AMR) AF: 0.557 AC: 24874 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 18677 AN: 26080

East Asian (EAS) AF: 0.667 AC: 26467 AN: 39660

South Asian (SAS) AF: 0.688 AC: 59250 AN: 86126

European-Finnish (FIN) AF: 0.631 AC: 33247 AN: 52690

Middle Eastern (MID) AF: 0.716 AC: 3773 AN: 5272

European-Non Finnish (NFE) AF: 0.682 AC: 758042 AN: 1111252

Other (OTH) AF: 0.660 AC: 39741 AN: 60248

GnomAD4 genome AF: 0.562 AC: 85514 AN: 152198 Hom.: 25933 Cov.: 35 AF XY: 0.564 AC XY: 41952 AN XY: 74408

African (AFR) AF: 0.313 AC: 12980 AN: 41536

American (AMR) AF: 0.552 AC: 8444 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2494 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3417 AN: 5158

South Asian (SAS) AF: 0.672 AC: 3244 AN: 4826

European-Finnish (FIN) AF: 0.641 AC: 6791 AN: 10592

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46103 AN: 68000

Other (OTH) AF: 0.614 AC: 1299 AN: 2114

Alfa AF: 0.665 Hom.: 81886

Bravo AF: 0.545

TwinsUK AF: 0.681 AC: 2527

ALSPAC AF: 0.677 AC: 2608

ESP6500AA AF: 0.323 AC: 1422

ESP6500EA AF: 0.682 AC: 5866

ExAC AF: 0.634 AC: 76861

Asia WGS AF: 0.641 AC: 2229 AN: 3478

EpiCase AF: 0.691

EpiControl AF: 0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0000099	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.83
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.22	T
Sift4G	Benign	0.33	T
Polyphen		0.16	B
Vest4		0.088
MPC		0.28
ClinPred		0.064	T
GERP RS		4.8
Varity_R		0.068
gMVP		0.23
Mutation Taster		=85/15	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: rs2271275; hg19: chr10-1230968; COSMIC: COSV67181984;