chr10-1185028-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB2	NM_018702.4	c.1876G>A	p.Ala626Thr	missense_variant	Exon 9 of 10	ENST00000381312.6	NP_061172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB2	ENST00000381312.6	c.1876G>A	p.Ala626Thr	missense_variant	Exon 9 of 10	1	NM_018702.4	ENSP00000370713.1

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

GnomAD3 exomes AF: 0.639 AC: 157758 AN: 246950 Hom.: 51643 AF XY: 0.650 AC XY: 87118 AN XY: 134088

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 SAS exome AF: 0.686

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

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.688

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.660

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.614

Alfa AF: 0.666 Hom.: 61144

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 v4.3

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;T;T
MetaRNN	Benign	0.0000099	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.16	B;.;B
Vest4		0.088
MPC		0.28
ClinPred		0.064	T
GERP RS		4.8
Varity_R		0.068
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs2271275; hg19: chr10-1230968; COSMIC: COSV67181984;