rs6685568

Variant names:

• chr1-67389614-A-G
• rs6685568
• NM_001374259.2:c.1947-415A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-67389614-A-G
• chr1-67389614-A-T

Variant summary

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

The NM_001374259.2(IL12RB2):​c.1947-415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,102 control chromosomes in the GnomAD database, including 2,204 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 0.14 (2204 hom., cov: 32)
• Consequence: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2	c.1947-415A>G		intron_variant	Intron 15 of 16	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2	c.1947-415A>G		intron_variant	Intron 15 of 16		NM_001374259.2	ENSP00000501329.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21036 AN: 151986 Hom.: 2192 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.139 AC: 21092 AN: 152102 Hom.: 2204 Cov.: 32 AF XY: 0.138 AC XY: 10242 AN XY: 74364

African (AFR) AF: 0.281 AC: 11667 AN: 41476

American (AMR) AF: 0.154 AC: 2349 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5172

South Asian (SAS) AF: 0.0977 AC: 471 AN: 4820

European-Finnish (FIN) AF: 0.0467 AC: 495 AN: 10590

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4208 AN: 67988

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.111 Hom.: 297

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

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: rs6685568; hg19: chr1-67855297;