rs11265611

Variant names:

• chr1-154422649-G-A
• rs11265611
• NM_000565.4:c.86-6547G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-154422649-G-A
• chr1-154422649-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000565.4(IL6R):​c.86-6547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,026 control chromosomes in the GnomAD database, including 26,211 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 0.58 (26211 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 10 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-6547G>A		intron_variant	Intron 1 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.86-6547G>A		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.86-6547G>A		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.86-6547G>A		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.86-6547G>A		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88753 AN: 151908 Hom.: 26174 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.584 AC: 88845 AN: 152026 Hom.: 26211 Cov.: 32 AF XY: 0.577 AC XY: 42857 AN XY: 74328

African (AFR) AF: 0.589 AC: 24436 AN: 41478

American (AMR) AF: 0.665 AC: 10162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2060 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2556 AN: 5168

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4824

European-Finnish (FIN) AF: 0.457 AC: 4837 AN: 10576

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40316 AN: 67926

Other (OTH) AF: 0.576 AC: 1210 AN: 2100

Alfa AF: 0.577 Hom.: 3158

Bravo AF: 0.605

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11265611; hg19: chr1-154395125;