rs2069835

Variant names:

• chr7-22728252-T-C
• rs2069835
• NM_000600.5:c.211-441T>C

Variant summary

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

The NM_000600.5(IL6):​c.211-441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,194 control chromosomes in the GnomAD database, including 478 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 0.075 (478 hom., cov: 32)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.999
• Publications: 40 publications found

Genes affected

IL6 (HGNC:6018): (interleukin 6) This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2). [provided by RefSeq, Aug 2020]

IL6 Gene-Disease associations (from GenCC):

• Kaposi sarcoma, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000600.5. 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
	IL6	NM_000600.5	MANE Select	c.211-441T>C		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.142-441T>C		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-18-441T>C		intron	N/A	NP_001305024.1	B5MC21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.211-441T>C		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.373-441T>C		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.211-441T>C		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11447 AN: 152076 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0752 AC: 11447 AN: 152194 Hom.: 478 Cov.: 32 AF XY: 0.0763 AC XY: 5681 AN XY: 74410

African (AFR) AF: 0.101 AC: 4178 AN: 41510

American (AMR) AF: 0.0540 AC: 825 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0674 AC: 325 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1329 AN: 10592

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.0590 AC: 4012 AN: 68012

Other (OTH) AF: 0.0737 AC: 156 AN: 2116

Alfa AF: 0.0705 Hom.: 533

Bravo AF: 0.0733

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.49
PhyloP100		1.0
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: rs2069835; hg19: chr7-22767871;