NM_000628.5:c.49+19G>A

Variant names:

• chr21-33266533-G-A
• rs559874353
• NM_000628.5:c.49+19G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000628.5(IL10RB):​c.49+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,540,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.177
• Publications: 0 publications found

Genes affected

IL10RB (HGNC:5965): (interleukin 10 receptor subunit beta) The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008]

IFNAR2-IL10RB (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 21-33266533-G-A is Benign according to our data. Variant chr21-33266533-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1923430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000263 (4/152360) while in subpopulation SAS AF = 0.000828 (4/4832). AF 95% confidence interval is 0.000282. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000628.5. 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
	IL10RB	NM_000628.5	MANE Select	c.49+19G>A		intron	N/A	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.710-1861G>A		intron	N/A	NP_001401434.1	H0Y3Z8
	IL10RB	NM_001405850.1		c.49+19G>A		intron	N/A	NP_001392779.1	A0A1B0GU52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.49+19G>A		intron	N/A	ENSP00000290200.2	Q08334
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.710-1861G>A		intron	N/A	ENSP00000388223.3	H0Y3Z8
	IL10RB	ENST00000896213.1		c.49+19G>A		intron	N/A	ENSP00000566272.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000636 AC: 9 AN: 141486 AF XY: 0.0000794

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000216 AC: 30 AN: 1388340 Hom.: 0 Cov.: 31 AF XY: 0.0000306 AC XY: 21 AN XY: 685312

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25152

East Asian (EAS) AF: 0.00 AC: 0 AN: 35828

South Asian (SAS) AF: 0.000354 AC: 28 AN: 79198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4920

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078516

Other (OTH) AF: 0.0000346 AC: 2 AN: 57846

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152360 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

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: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000508 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inflammatory bowel disease 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.0
DANN	Uncertain	0.98
PhyloP100		-0.18
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs559874353; hg19: chr21-34638838;