rs7549338

Variant names:

• chr1-154431904-C-G
• rs7549338
• NM_000565.4:c.458+1298C>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.458+1298C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,052 control chromosomes in the GnomAD database, including 27,274 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 0.59 (27274 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 26 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.458+1298C>G		intron_variant	Intron 3 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.458+1298C>G		intron_variant	Intron 3 of 9	1	NM_000565.4	ENSP00000357470.3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90242 AN: 151934 Hom.: 27226 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.594 AC: 90347 AN: 152052 Hom.: 27274 Cov.: 32 AF XY: 0.585 AC XY: 43465 AN XY: 74324

African (AFR) AF: 0.664 AC: 27529 AN: 41448

American (AMR) AF: 0.659 AC: 10057 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2021 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2470 AN: 5168

South Asian (SAS) AF: 0.461 AC: 2225 AN: 4828

European-Finnish (FIN) AF: 0.459 AC: 4853 AN: 10582

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39142 AN: 67974

Other (OTH) AF: 0.581 AC: 1227 AN: 2112

Alfa AF: 0.580 Hom.: 3208

Bravo AF: 0.617

Asia WGS AF: 0.482 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.59
PhyloP100		-0.51
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: rs7549338; hg19: chr1-154404380;