dbSNP rs1254033245: IL6R:c.86-20G>A (chr1-154429176-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000565.4(IL6R):c.86-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,448,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

IL6R
NM_000565.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.471

Publications

0 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

IL6R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-154429176-G-A is Benign according to our data. Variant chr1-154429176-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3620890.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000565.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL6R	NM_000565.4	MANE Select	c.86-20G>A	intron	N/A	NP_000556.1	P08887-1
IL6R	NM_001382769.1		c.86-20G>A	intron	N/A	NP_001369698.1
IL6R	NM_001382770.1		c.86-20G>A	intron	N/A	NP_001369699.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL6R	ENST00000368485.8	TSL:1 MANE Select	c.86-20G>A	intron	N/A	ENSP00000357470.3	P08887-1
IL6R	ENST00000344086.8	TSL:1	c.86-20G>A	intron	N/A	ENSP00000340589.4	P08887-2
IL6R	ENST00000622330.5	TSL:1	c.86-20G>A	intron	N/A	ENSP00000477739.1	A0A087WTB5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248804

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000387

AC:

AN:

1448184

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

717242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.00

AC:

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

39240

South Asian (SAS)

AF:

0.00

AC:

AN:

85722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.0000500

AC:

AN:

1101036

Other (OTH)

AF:

0.0000168

AC:

AN:

59700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

(source)

DANN

Benign

0.53

PhyloP100

-0.47

PromoterAI

0.0026

Neutral

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over