chr10-1184934-C-T

Variant names:

• chr10-1184934-C-T
• rs141298814
• NM_018702.4:c.1970G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018702.4(ADARB2):​c.1970G>A​(p.Arg657Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,613,926 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00043 (8 hom.)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.569
• Publications: 5 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008507669).
• BP6: Variant 10-1184934-C-T is Benign according to our data. Variant chr10-1184934-C-T is described in ClinVar as Benign. ClinVar VariationId is 790273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.1970G>A	p.Arg657Gln	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.1970G>A	p.Arg657Gln	missense	Exon 9 of 10	ENSP00000370713.1	Q9NS39-1
	ADARB2	ENST00000381310.7	TSL:1	c.497G>A	p.Arg166Gln	missense	Exon 2 of 3	ENSP00000370711.3	Q9NS39-2
	ADARB2	ENST00000474762.5	TSL:1	n.170G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 503 AN: 152252 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00124 AC: 311 AN: 250442 AF XY: 0.00101

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000430 AC: 629 AN: 1461556 Hom.: 8 Cov.: 30 AF XY: 0.000381 AC XY: 277 AN XY: 727110

African (AFR) AF: 0.0128 AC: 429 AN: 33476

American (AMR) AF: 0.000514 AC: 23 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00219 AC: 87 AN: 39694

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5746

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111998

Other (OTH) AF: 0.000944 AC: 57 AN: 60390

GnomAD4 genome AF: 0.00330 AC: 503 AN: 152370 Hom.: 4 Cov.: 34 AF XY: 0.00334 AC XY: 249 AN XY: 74518

African (AFR) AF: 0.0108 AC: 449 AN: 41598

American (AMR) AF: 0.00131 AC: 20 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00502 AC: 26 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00132 Hom.: 4

Bravo AF: 0.00382

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00126 AC: 153

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0085	T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.57
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.46	P
Vest4		0.27
MVP		0.44
MPC		0.62
ClinPred		0.047	T
GERP RS		-3.0
Varity_R		0.27
gMVP		0.41
Mutation Taster		=96/4	polymorphism

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: rs141298814; hg19: chr10-1230874; COSMIC: COSV67182069;