dbSNP rs4379670: IL6R:c.*2009T>A (chr1-154467389-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000565.4(IL6R):c.*2009T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,100 control chromosomes in the GnomAD database, including 48,301 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 0.80 ( 48296 hom., cov: 31)

Exomes 𝑓: 0.71 ( 5 hom. )

Consequence

IL6R
NM_000565.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

hyper-IgE recurrent infection syndrome 5, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

IL6R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4 link	c.*2009T>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000368485.8	NP_000556.1	P08887-1A0N0L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8 link	c.*2009T>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_000565.4	ENSP00000357470.3		P08887-1

Frequencies

GnomAD3 genomes

AF:

0.795

AC:

120883

AN:

151968

Hom.:

48243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.840

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.828

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.808

GnomAD4 exome

AF:

0.714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.796

AC:

120994

AN:

152086

Hom.:

48296

Cov.:

AF XY:

0.790

AC XY:

58678

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.792

AC:

32832

AN:

41476

American (AMR)

AF:

0.840

AC:

12834

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

2866

AN:

3470

East Asian (EAS)

AF:

0.821

AC:

4255

AN:

5180

South Asian (SAS)

AF:

0.768

AC:

3701

AN:

4818

European-Finnish (FIN)

AF:

0.667

AC:

7044

AN:

10558

Middle Eastern (MID)

AF:

0.829

AC:

242

AN:

292

European-Non Finnish (NFE)

AF:

0.805

AC:

54716

AN:

67994

Other (OTH)

AF:

0.809

AC:

1708

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1244

2488

3733

4977

6221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.789

Hom.:

5842

Bravo

AF:

0.811

Asia WGS

AF:

0.772

AC:

2687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.42

(source)

DANN

Benign

0.65

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over