NM_000565.4:c.1160+3035C>T

Variant names:

• chr1-154457616-C-T
• rs11265618
• NM_000565.4:c.1160+3035C>T

Variant summary

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

The NM_000565.4(IL6R):​c.1160+3035C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,112 control chromosomes in the GnomAD database, including 3,856 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 0.21 (3856 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 49 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.1160+3035C>T		intron_variant	Intron 9 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.1160+3035C>T		intron_variant	Intron 9 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.1067-7518C>T		intron_variant	Intron 8 of 8	1		ENSP00000340589.4
IL6R	ENST00000502679.1	n.473+3035C>T		intron_variant	Intron 1 of 1	2
IL6R	ENST00000507256.1	n.358+3035C>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32078 AN: 151994 Hom.: 3839 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.211 AC: 32131 AN: 152112 Hom.: 3856 Cov.: 32 AF XY: 0.209 AC XY: 15533 AN XY: 74358

African (AFR) AF: 0.330 AC: 13666 AN: 41464

American (AMR) AF: 0.140 AC: 2132 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5180

South Asian (SAS) AF: 0.179 AC: 865 AN: 4824

European-Finnish (FIN) AF: 0.167 AC: 1767 AN: 10584

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11832 AN: 67990

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.183 Hom.: 5625

Bravo AF: 0.212

Asia WGS AF: 0.181 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		-0.81
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: rs11265618; hg19: chr1-154430092;