rs8178571

Positions:

• chr21-33298166-A-G

Variant summary

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

The NM_001405850.1(IL10RB):​c.804+9905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,236 control chromosomes in the GnomAD database, including 854 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 0.057 (854 hom., cov: 32)
• Consequence: IL10RB NM_001405850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL10RB	NM_001405849.1	c.804+9905A>G		intron_variant			NP_001392778.1
IL10RB	NM_001405850.1	c.804+9905A>G		intron_variant			NP_001392779.1
IL10RB	NR_175973.1	n.745+9905A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000609556.3	c.804+9905A>G		intron_variant		5		ENSP00000489965	A2
IL10RB	ENST00000637650.2	c.804+9905A>G		intron_variant		5		ENSP00000489716	A2

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8633 AN: 152118 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0568 AC: 8651 AN: 152236 Hom.: 854 Cov.: 32 AF XY: 0.0541 AC XY: 4025 AN XY: 74446

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0223 Hom.: 87

Bravo AF: 0.0647

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8178571; hg19: chr21-34670471;