rs999788

Positions:

• chr21-33265726-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414505.1(IFNAR2-IL10RB):​c.710-2668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 273,880 control chromosomes in the GnomAD database, including 8,393 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 0.21 (3900 hom., cov: 31)
  • Exomes 𝑓: 0.25 (4493 hom.)
• Consequence: IFNAR2-IL10RB NM_001414505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

Genes affected

IFNAR2-IL10RB (HGNC:):

IL10RB-DT (HGNC:44303): (IL10RB divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNAR2-IL10RB	NM_001414505.1	c.710-2668C>T		intron_variant
IL10RB-DT	NR_038974.1	n.375G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL10RB-DT	ENST00000411998.3	n.411G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31574 AN: 151594 Hom.: 3897 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.246 AC: 30029 AN: 122168 Hom.: 4493 Cov.: 0 AF XY: 0.264 AC XY: 18326 AN XY: 69480

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.208 AC: 31595 AN: 151712 Hom.: 3900 Cov.: 31 AF XY: 0.218 AC XY: 16128 AN XY: 74136

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.209

Alfa AF: 0.198 Hom.: 692

Bravo AF: 0.209

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.67

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: rs999788; hg19: chr21-34638031; COSMIC: COSV51615456;