rs2228420

Variant names:

• chr1-67386652-G-A
• rs2228420
• NM_001374259.2:c.1929G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-67386652-G-A
• chr1-67386652-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000674203.2(IL12RB2):​c.1929G>A​(p.Thr643Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,607,342 control chromosomes in the GnomAD database, including 259,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (18804 hom., cov: 29)
  • Exomes 𝑓: 0.57 (240265 hom.)
• Consequence: IL12RB2 ENST00000674203.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.599
• Publications: 22 publications found

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-67386652-G-A is Benign according to our data. Variant chr1-67386652-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.599 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674203.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.1929G>A	p.Thr643Thr	synonymous	Exon 15 of 17	NP_001361188.1
	IL12RB2	NM_001559.3		c.1929G>A	p.Thr643Thr	synonymous	Exon 14 of 16	NP_001550.1
	IL12RB2	NM_001258215.1		c.1671G>A	p.Thr557Thr	synonymous	Exon 12 of 14	NP_001245144.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.1929G>A	p.Thr643Thr	synonymous	Exon 15 of 17	ENSP00000501329.1
	IL12RB2	ENST00000262345.5	TSL:1	c.1929G>A	p.Thr643Thr	synonymous	Exon 14 of 16	ENSP00000262345.1
	IL12RB2	ENST00000544434.5	TSL:1	c.1671G>A	p.Thr557Thr	synonymous	Exon 12 of 14	ENSP00000442443.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71023 AN: 151432 Hom.: 18801 Cov.: 29

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.454

GnomAD2 exomes AF: 0.528 AC: 132759 AN: 251390 AF XY: 0.539

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.336

Gnomad FIN exome AF: 0.692

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.568 AC: 827042 AN: 1455794 Hom.: 240265 Cov.: 31 AF XY: 0.569 AC XY: 412601 AN XY: 724690

African (AFR) AF: 0.213 AC: 7097 AN: 33394

American (AMR) AF: 0.478 AC: 21373 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 11799 AN: 26096

East Asian (EAS) AF: 0.360 AC: 14268 AN: 39644

South Asian (SAS) AF: 0.574 AC: 49482 AN: 86164

European-Finnish (FIN) AF: 0.683 AC: 36473 AN: 53390

Middle Eastern (MID) AF: 0.502 AC: 2888 AN: 5748

European-Non Finnish (NFE) AF: 0.589 AC: 651503 AN: 1106492

Other (OTH) AF: 0.535 AC: 32159 AN: 60158

GnomAD4 genome AF: 0.469 AC: 71031 AN: 151548 Hom.: 18804 Cov.: 29 AF XY: 0.475 AC XY: 35156 AN XY: 74026

African (AFR) AF: 0.230 AC: 9465 AN: 41234

American (AMR) AF: 0.465 AC: 7081 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1541 AN: 3464

East Asian (EAS) AF: 0.344 AC: 1766 AN: 5128

South Asian (SAS) AF: 0.563 AC: 2712 AN: 4814

European-Finnish (FIN) AF: 0.697 AC: 7324 AN: 10506

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39565 AN: 67888

Other (OTH) AF: 0.449 AC: 941 AN: 2094

Alfa AF: 0.538 Hom.: 56080

Bravo AF: 0.435

Asia WGS AF: 0.390 AC: 1358 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs2228420; hg19: chr1-67852335; COSMIC: COSV52022013;