Genetic Variant NM_000565.4:c.1161-1206C>G (chr1-154463928-C-G) – 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.1161-1206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,950 control chromosomes in the GnomAD database, including 35,765 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 0.67 ( 35765 hom., cov: 30)

Consequence

IL6R
NM_000565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940

Publications

11 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4 link	c.1161-1206C>G		intron_variant	Intron 9 of 9	ENST00000368485.8	NP_000556.1	P08887-1A0N0L5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL6R	ENST00000368485.8 link	c.1161-1206C>G	intron_variant	Intron 9 of 9	1	NM_000565.4	ENSP00000357470.3	P08887-1
IL6R	ENST00000344086.8 link	c.1067-1206C>G	intron_variant	Intron 8 of 8	1		ENSP00000340589.4	P08887-2
IL6R	ENST00000502679.1 link	n.474-1206C>G	intron_variant	Intron 1 of 1	2
IL6R	ENST00000507256.1 link	n.359-1206C>G	intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102018

AN:

151832

Hom.:

35751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.774

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.826

Gnomad SAS

AF:

0.758

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.672

AC:

102077

AN:

151950

Hom.:

35765

Cov.:

AF XY:

0.670

AC XY:

49795

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.462

AC:

19129

AN:

41422

American (AMR)

AF:

0.774

AC:

11810

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2709

AN:

3470

East Asian (EAS)

AF:

0.826

AC:

4255

AN:

5150

South Asian (SAS)

AF:

0.759

AC:

3656

AN:

4820

European-Finnish (FIN)

AF:

0.628

AC:

6619

AN:

10540

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.757

AC:

51459

AN:

67972

Other (OTH)

AF:

0.700

AC:

1476

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1497

2994

4492

5989

7486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.694

Hom.:

4683

Bravo

AF:

0.678

Asia WGS

AF:

0.740

AC:

2573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.57

PhyloP100

-0.094

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over