Genetic Variant NM_000565.4:c.1160+4985G>C (chr1-154459566-G-C) – 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.1160+4985G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,102 control chromosomes in the GnomAD database, including 40,400 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 0.73 ( 40400 hom., cov: 32)

Consequence

IL6R
NM_000565.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.116

Publications

19 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=-1.03).

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.1160+4985G>C		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.1160+4985G>C	intron_variant	Intron 9 of 9	1	NM_000565.4	ENSP00000357470.3	P08887-1
IL6R	ENST00000344086.8 link	c.1067-5568G>C	intron_variant	Intron 8 of 8	1		ENSP00000340589.4	P08887-2
IL6R	ENST00000502679.1 link	n.473+4985G>C	intron_variant	Intron 1 of 1	2
IL6R	ENST00000507256.1 link	n.358+4985G>C	intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110295

AN:

151984

Hom.:

40367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.826

Gnomad SAS

AF:

0.755

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.732

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

GnomAD4 genome

AF:

0.726

AC:

110383

AN:

152102

Hom.:

40400

Cov.:

AF XY:

0.721

AC XY:

53638

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.650

AC:

26967

AN:

41492

American (AMR)

AF:

0.791

AC:

12092

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

2717

AN:

3472

East Asian (EAS)

AF:

0.826

AC:

4277

AN:

5180

South Asian (SAS)

AF:

0.756

AC:

3644

AN:

4822

European-Finnish (FIN)

AF:

0.630

AC:

6648

AN:

10556

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.758

AC:

51523

AN:

67982

Other (OTH)

AF:

0.732

AC:

1546

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1566

3132

4697

6263

7829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.728

Hom.:

5026

Bravo

AF:

0.738

Asia WGS

AF:

0.751

AC:

2613

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.8

(source)

DANN

Benign

0.43

PhyloP100

0.12

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