21-33299227-T-C

Variant names:

• chr21-33299227-T-C
• rs8134731
• NM_001405850.1:c.805-8958T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405850.1(IL10RB):​c.805-8958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,938 control chromosomes in the GnomAD database, including 3,932 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 0.22 (3932 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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]

IL10RB Gene-Disease associations (from GenCC):

• inflammatory bowel disease 25

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000294417 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_001405850.1	c.805-8958T>C		intron_variant	Intron 6 of 6		NP_001392779.1
IL10RB	NM_001405849.1	c.805-9749T>C		intron_variant	Intron 6 of 6		NP_001392778.1
IL10RB	NR_175973.1	n.746-9749T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000609556.3	c.805-8958T>C		intron_variant	Intron 6 of 6	5		ENSP00000489965.2
IL10RB	ENST00000637650.2	c.805-9749T>C		intron_variant	Intron 6 of 6	5		ENSP00000489716.2
ENSG00000294417	ENST00000723465.1	n.301-280A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33960 AN: 151820 Hom.: 3928 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 33983 AN: 151938 Hom.: 3932 Cov.: 32 AF XY: 0.225 AC XY: 16721 AN XY: 74256

African (AFR) AF: 0.272 AC: 11282 AN: 41428

American (AMR) AF: 0.187 AC: 2858 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 428 AN: 3464

East Asian (EAS) AF: 0.384 AC: 1980 AN: 5152

South Asian (SAS) AF: 0.244 AC: 1173 AN: 4814

European-Finnish (FIN) AF: 0.252 AC: 2651 AN: 10540

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12952 AN: 67946

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.210 Hom.: 518

Bravo AF: 0.223

Asia WGS AF: 0.354 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.57
PhyloP100		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8134731; hg19: chr21-34671532;