1-154458929-C-A

Variant names:

• chr1-154458929-C-A
• rs10159236
• NM_000565.4:c.1160+4348C>A

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+4348C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,354 control chromosomes in the GnomAD database, including 1,942 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 (1942 hom., cov: 31)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	NM_000565.4	MANE Select	c.1160+4348C>A		intron	N/A	NP_000556.1
	IL6R	NM_001382769.1		c.1259+4348C>A		intron	N/A	NP_001369698.1
	IL6R	NM_001382770.1		c.1253+4348C>A		intron	N/A	NP_001369699.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.1160+4348C>A		intron	N/A	ENSP00000357470.3
	IL6R	ENST00000344086.8	TSL:1	c.1067-6205C>A		intron	N/A	ENSP00000340589.4
	IL6R	ENST00000502679.1	TSL:2	n.473+4348C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23790 AN: 151250 Hom.: 1936 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.157 AC: 23810 AN: 151354 Hom.: 1942 Cov.: 31 AF XY: 0.156 AC XY: 11553 AN XY: 73880

African (AFR) AF: 0.167 AC: 6888 AN: 41198

American (AMR) AF: 0.115 AC: 1746 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3468

East Asian (EAS) AF: 0.104 AC: 537 AN: 5158

South Asian (SAS) AF: 0.179 AC: 859 AN: 4798

European-Finnish (FIN) AF: 0.146 AC: 1512 AN: 10354

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11083 AN: 67888

Other (OTH) AF: 0.151 AC: 315 AN: 2088

Alfa AF: 0.105 Hom.: 182

Bravo AF: 0.153

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
DANN	Benign	0.44
PhyloP100		-0.14
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: rs10159236; hg19: chr1-154431405; COSMIC: COSV59819702; COSMIC: COSV59819702;