NM_000628.5:c.647-754_647-751dupGTTT

Variant names:

• chr21-33287341-G-GGTTT
• rs1610997
• NM_000628.5:c.647-754_647-751dupGTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000628.5(IL10RB):​c.647-754_647-751dupGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20561 hom., cov: 0)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• 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

IFNAR2-IL10RB (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL10RB	NM_000628.5	c.647-754_647-751dupGTTT		intron_variant	Intron 5 of 6	ENST00000290200.7	NP_000619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10RB	ENST00000290200.7	c.647-763_647-762insGTTT		intron_variant	Intron 5 of 6	1	NM_000628.5	ENSP00000290200.2
IFNAR2-IL10RB	ENST00000433395.7	c.1307-763_1307-762insGTTT		intron_variant	Intron 11 of 12	5		ENSP00000388223.3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76458 AN: 150756 Hom.: 20525 Cov.: 0

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.507 AC: 76533 AN: 150872 Hom.: 20561 Cov.: 0 AF XY: 0.502 AC XY: 37028 AN XY: 73710

African (AFR) AF: 0.693 AC: 28378 AN: 40922

American (AMR) AF: 0.407 AC: 6191 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1931 AN: 3462

East Asian (EAS) AF: 0.207 AC: 1061 AN: 5138

South Asian (SAS) AF: 0.374 AC: 1784 AN: 4776

European-Finnish (FIN) AF: 0.469 AC: 4871 AN: 10382

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30739 AN: 67694

Other (OTH) AF: 0.482 AC: 1014 AN: 2102

Alfa AF: 0.305 Hom.: 606

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1610997; hg19: chr21-34659646;