Variant 1-67329636-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001374259.2(IL12RB2):c.714T>C(p.Ser238=) 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 (★★).

Frequency

Genomes: 𝑓 0.90 ( 62696 hom., cov: 31)

Exomes 𝑓: 0.97 ( 666298 hom. )

Consequence

IL12RB2
NM_001374259.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

Variant links:

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]

IL12RB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 1-67329636-T-C is Benign according to our data. Variant chr1-67329636-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB2	NM_001374259.2 linkuse as main transcript	c.714T>C	p.Ser238=	synonymous_variant	7/17	ENST00000674203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB2	ENST00000674203.2 linkuse as main transcript	c.714T>C	p.Ser238=	synonymous_variant	7/17		NM_001374259.2	P1	Q99665-1

Frequencies

GnomAD3 genomes

AF:

0.902

AC:

137165

AN:

152066

Hom.:

62664

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.931

AC:

234185

AN:

251450

Hom.:

109813

AF XY:

0.938

AC XY:

127532

AN XY:

135898

show subpopulations

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 SAS exome

AF:

0.925

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.:

AF XY:

0.967

AC XY:

685994

AN XY:

709262

show subpopulations

Gnomad4 AFR exome

AF:

0.741

Gnomad4 AMR exome

AF:

0.871

Gnomad4 ASJ exome

AF:

0.978

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.930

Gnomad4 FIN exome

AF:

0.979

Gnomad4 NFE exome

AF:

0.988

Gnomad4 OTH exome

AF:

0.944

GnomAD4 genome

AF:

0.902

AC:

137254

AN:

152184

Hom.:

62696

Cov.:

AF XY:

0.901

AC XY:

67036

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.896

Gnomad4 ASJ

AF:

0.978

Gnomad4 EAS

AF:

0.785

Gnomad4 SAS

AF:

0.918

Gnomad4 FIN

AF:

0.980

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.901

Alfa

AF:

0.957

Hom.:

91150

Bravo

AF:

0.887

EpiCase

AF:

0.985

EpiControl

AF:

0.983

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.30

DANN

Benign

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over