Variant 1-154465420-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000565.4(IL6R):c.*40T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,609,068 control chromosomes in the GnomAD database, including 522,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.79 ( 48250 hom., cov: 32)

Exomes 𝑓: 0.81 ( 473854 hom. )

Consequence

IL6R
NM_000565.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.02

Variant links:

Genes affected

IL6R (HGNC:6019): (interleukin 6 receptor) This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

IL6R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-154465420-T-C is Benign according to our data. Variant chr1-154465420-T-C is described in ClinVar as [Benign]. Clinvar id is 2688366.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4 link	c.*40T>C		3_prime_UTR_variant	10/10	ENST00000368485.8	NP_000556.1	P08887-1A0N0L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8 link	c.*40T>C		3_prime_UTR_variant	10/10	1	NM_000565.4	ENSP00000357470.3		P08887-1
IL6R	ENST00000344086.8 link	c.*255T>C		3_prime_UTR_variant	9/9	1		ENSP00000340589.4		P08887-2

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120859

AN:

152074

Hom.:

48197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.840

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.807

GnomAD3 exomes

AF:

0.797

AC:

196608

AN:

246786

Hom.:

78691

AF XY:

0.795

AC XY:

106516

AN XY:

134064

show subpopulations

Gnomad AFR exome

AF:

0.792

Gnomad AMR exome

AF:

0.831

Gnomad ASJ exome

AF:

0.818

Gnomad EAS exome

AF:

0.840

Gnomad SAS exome

AF:

0.782

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.806

AC:

1173727

AN:

1456876

Hom.:

473854

Cov.:

AF XY:

0.804

AC XY:

582154

AN XY:

724240

show subpopulations

Gnomad4 AFR exome

AF:

0.791

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.823

Gnomad4 EAS exome

AF:

0.828

Gnomad4 SAS exome

AF:

0.780

Gnomad4 FIN exome

AF:

0.680

Gnomad4 NFE exome

AF:

0.812

Gnomad4 OTH exome

AF:

0.803

GnomAD4 genome

AF:

0.795

AC:

120970

AN:

152192

Hom.:

48250

Cov.:

AF XY:

0.789

AC XY:

58678

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.840

Gnomad4 ASJ

AF:

0.824

Gnomad4 EAS

AF:

0.823

Gnomad4 SAS

AF:

0.775

Gnomad4 FIN

AF:

0.665

Gnomad4 NFE

AF:

0.803

Gnomad4 OTH

AF:

0.808

Alfa

AF:

0.810

Hom.:

93710

Bravo

AF:

0.811

Asia WGS

AF:

0.779

AC:

2710

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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: 87. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.030

DANN

Benign

0.43

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