rs1386821

Variant names:

• chr1-154409573-T-G
• rs1386821
• NM_000565.4:c.85+3859T>G

Variant summary

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

The NM_000565.4(IL6R):​c.85+3859T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,156 control chromosomes in the GnomAD database, including 2,139 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 0.16 (2139 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 38 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.85+3859T>G		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.85+3859T>G		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.85+3859T>G		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.85+3859T>G		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.85+3859T>G		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24146 AN: 152038 Hom.: 2140 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.159 AC: 24152 AN: 152156 Hom.: 2139 Cov.: 31 AF XY: 0.159 AC XY: 11814 AN XY: 74368

African (AFR) AF: 0.109 AC: 4547 AN: 41526

American (AMR) AF: 0.138 AC: 2112 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5182

South Asian (SAS) AF: 0.141 AC: 680 AN: 4824

European-Finnish (FIN) AF: 0.219 AC: 2312 AN: 10568

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13216 AN: 67974

Other (OTH) AF: 0.134 AC: 284 AN: 2116

Alfa AF: 0.179 Hom.: 5055

Bravo AF: 0.149

Asia WGS AF: 0.0920 AC: 319 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	4.1
DANN	Benign	0.57
PhyloP100		0.17
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: rs1386821; hg19: chr1-154382049;