10-1233818-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_018702.4(ADARB2):c.1389G>A(p.Ser463=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,988 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (20 hom., cov: 30)
  • Exomes 𝑓: 0.00086 (9 hom.)
• Consequence: ADARB2 NM_018702.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.940

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-1233818-C-T is Benign according to our data. Variant chr10-1233818-C-T is described in ClinVar as [Benign]. Clinvar id is 789439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00623 (948/152170) while in subpopulation AFR AF= 0.0213 (883/41484). AF 95% confidence interval is 0.0201. There are 20 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB2	NM_018702.4	c.1389G>A	p.Ser463=	synonymous_variant	6/10	ENST00000381312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB2	ENST00000381312.6	c.1389G>A	p.Ser463=	synonymous_variant	6/10	1	NM_018702.4	P1
LINC00200	ENST00000655745.1	n.265-54655C>T		intron_variant, non_coding_transcript_variant
ADARB2	ENST00000469464.1	n.173G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.00622 AC: 946 AN: 152052 Hom.: 20 Cov.: 30

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00209 AC: 526 AN: 251360 Hom.: 5 AF XY: 0.00156 AC XY: 212 AN XY: 135852

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00130

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000864 AC: 1263 AN: 1461818 Hom.: 9 Cov.: 33 AF XY: 0.000769 AC XY: 559 AN XY: 727204

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00214

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.000599

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00623 AC: 948 AN: 152170 Hom.: 20 Cov.: 30 AF XY: 0.00594 AC XY: 442 AN XY: 74380

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00263 Hom.: 2

Bravo AF: 0.00733

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.14
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35356097; hg19: chr10-1279760;