rs2229238

Variant names:

• chr1-154465420-T-C
• rs2229238
• NM_000565.4:c.*40T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-154465420-T-C
• chr1-154465420-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000565.4(IL6R):​c.*40T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,609,068 control chromosomes in the GnomAD database, including 522,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.79 (48250 hom., cov: 32)
  • Exomes 𝑓: 0.81 (473854 hom.)
• Consequence: IL6R NM_000565.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.02
• Publications: 85 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-154465420-T-C is Benign according to our data. Variant chr1-154465420-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.827 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	NM_000565.4	MANE Select	c.*40T>C		3_prime_UTR	Exon 10 of 10	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.*40T>C		3_prime_UTR	Exon 11 of 11	NP_001369698.1
	IL6R	NM_001382770.1		c.*40T>C		3_prime_UTR	Exon 11 of 11	NP_001369699.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.*40T>C		3_prime_UTR	Exon 10 of 10	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.*255T>C		3_prime_UTR	Exon 9 of 9	ENSP00000340589.4	P08887-2
	IL6R	ENST00000858510.1		c.*40T>C		3_prime_UTR	Exon 12 of 12	ENSP00000528569.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120859 AN: 152074 Hom.: 48197 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.807

GnomAD2 exomes AF: 0.797 AC: 196608 AN: 246786 AF XY: 0.795

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.818

Gnomad EAS exome AF: 0.840

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.803

GnomAD4 exome AF: 0.806 AC: 1173727 AN: 1456876 Hom.: 473854 Cov.: 34 AF XY: 0.804 AC XY: 582154 AN XY: 724240

African (AFR) AF: 0.791 AC: 26381 AN: 33344

American (AMR) AF: 0.834 AC: 37226 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 21437 AN: 26060

East Asian (EAS) AF: 0.828 AC: 32772 AN: 39598

South Asian (SAS) AF: 0.780 AC: 67184 AN: 86136

European-Finnish (FIN) AF: 0.680 AC: 36087 AN: 53058

Middle Eastern (MID) AF: 0.807 AC: 4647 AN: 5760

European-Non Finnish (NFE) AF: 0.812 AC: 899615 AN: 1108040

Other (OTH) AF: 0.803 AC: 48378 AN: 60220

GnomAD4 genome AF: 0.795 AC: 120970 AN: 152192 Hom.: 48250 Cov.: 32 AF XY: 0.789 AC XY: 58678 AN XY: 74398

African (AFR) AF: 0.791 AC: 32866 AN: 41530

American (AMR) AF: 0.840 AC: 12841 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3472

East Asian (EAS) AF: 0.823 AC: 4260 AN: 5176

South Asian (SAS) AF: 0.775 AC: 3736 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7033 AN: 10578

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.803 AC: 54627 AN: 68000

Other (OTH) AF: 0.808 AC: 1710 AN: 2116

Alfa AF: 0.807 Hom.: 150239

Bravo AF: 0.811

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.43
PhyloP100		-5.0
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: rs2229238; hg19: chr1-154437896;