rs1495963

Variant names:

• chr1-67329636-T-C
• rs1495963
• NM_001374259.2:c.714T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-67329636-T-C
• chr1-67329636-T-A

Variant summary

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

The NM_001374259.2(IL12RB2):​c.714T>C​(p.Ser238Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,572,186 control chromosomes in the GnomAD database, including 728,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S238S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.90 (62696 hom., cov: 31)
  • Exomes 𝑓: 0.97 (666298 hom.)
• Consequence: IL12RB2 NM_001374259.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.27
• 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 (REVEL=0.006).
• BP6: Variant 1-67329636-T-C is Benign according to our data. Variant chr1-67329636-T-C is described in ClinVar as Benign. ClinVar VariationId is 1169787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 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.714T>C	p.Ser238Ser	synonymous	Exon 7 of 17	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.714T>C	p.Ser238Ser	synonymous	Exon 6 of 16	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.714T>C	p.Ser238Ser	synonymous	Exon 6 of 14	NP_001245144.1	Q99665-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.714T>C	p.Ser238Ser	synonymous	Exon 7 of 17	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.714T>C	p.Ser238Ser	synonymous	Exon 6 of 16	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.714T>C	p.Ser238Ser	synonymous	Exon 6 of 14	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137165 AN: 152066 Hom.: 62664 Cov.: 31

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.904

GnomAD2 exomes AF: 0.931 AC: 234185 AN: 251450 AF XY: 0.938

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.873

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 0.783

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.987

Gnomad OTH exome AF: 0.948

GnomAD4 exome AF: 0.967 AC: 1373196 AN: 1420002 Hom.: 666298 Cov.: 24 AF XY: 0.967 AC XY: 685994 AN XY: 709262

African (AFR) AF: 0.741 AC: 24165 AN: 32608

American (AMR) AF: 0.871 AC: 38911 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 25290 AN: 25868

East Asian (EAS) AF: 0.780 AC: 30801 AN: 39486

South Asian (SAS) AF: 0.930 AC: 79436 AN: 85438

European-Finnish (FIN) AF: 0.979 AC: 52306 AN: 53406

Middle Eastern (MID) AF: 0.946 AC: 5389 AN: 5694

European-Non Finnish (NFE) AF: 0.988 AC: 1061287 AN: 1073902

Other (OTH) AF: 0.944 AC: 55611 AN: 58932

GnomAD4 genome AF: 0.902 AC: 137254 AN: 152184 Hom.: 62696 Cov.: 31 AF XY: 0.901 AC XY: 67036 AN XY: 74396

African (AFR) AF: 0.752 AC: 31173 AN: 41480

American (AMR) AF: 0.896 AC: 13690 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3394 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4056 AN: 5164

South Asian (SAS) AF: 0.918 AC: 4424 AN: 4820

European-Finnish (FIN) AF: 0.980 AC: 10398 AN: 10614

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67033 AN: 68036

Other (OTH) AF: 0.901 AC: 1902 AN: 2110

Alfa AF: 0.950 Hom.: 110687

Bravo AF: 0.887

EpiCase AF: 0.985

EpiControl AF: 0.983

ClinVar

ClinVar submissions

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	-0.97
CADD	Benign	0.30
DANN	Benign	0.38
PhyloP100		-2.3
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: rs1495963; hg19: chr1-67795319; COSMIC: COSV52020395;