rs10489627

Variant names:

• chr1-67313993-A-G
• rs10489627
• NM_001374259.2:c.-44A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-67313993-A-G
• chr1-67313993-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.-44A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,084 control chromosomes in the GnomAD database, including 14,883 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 0.42 (14883 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: IL12RB2 NM_001374259.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 15 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374259.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	NM_001374259.2	MANE Select	c.-44A>G		5_prime_UTR	Exon 2 of 17	NP_001361188.1	Q99665-1
	IL12RB2	NM_001258214.1		c.-44A>G		5_prime_UTR	Exon 2 of 16	NP_001245143.1	B4DGA4
	IL12RB2	NM_001319233.1		c.-40A>G		5_prime_UTR	Exon 2 of 16	NP_001306162.1	B4DGA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.-44A>G		5_prime_UTR	Exon 2 of 17	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000541374.6	TSL:1	c.-44A>G		5_prime_UTR	Exon 2 of 13	ENSP00000445276.3	A0A0A0MTN7
	IL12RB2	ENST00000262345.5	TSL:1	c.-37+6026A>G		intron	N/A	ENSP00000262345.1	Q99665-1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63515 AN: 151960 Hom.: 14843 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.418 AC: 63610 AN: 152078 Hom.: 14883 Cov.: 32 AF XY: 0.412 AC XY: 30626 AN XY: 74354

African (AFR) AF: 0.637 AC: 26402 AN: 41442

American (AMR) AF: 0.400 AC: 6116 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5180

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4814

European-Finnish (FIN) AF: 0.244 AC: 2582 AN: 10590

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23072 AN: 67978

Other (OTH) AF: 0.440 AC: 929 AN: 2112

Alfa AF: 0.359 Hom.: 17086

Bravo AF: 0.442

Asia WGS AF: 0.357 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.82
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10489627;

hg19: chr1-67779676;