7-22728045-C-T

Variant names:

• chr7-22728045-C-T
• rs2069833
• NM_000600.5:c.210+411C>T

Variant summary

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

The NM_000600.5(IL6):​c.210+411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,126 control chromosomes in the GnomAD database, including 41,374 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 0.72 (41374 hom., cov: 32)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.210+411C>T		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.141+411C>T		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-18-648C>T		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.210+411C>T		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.372+411C>T		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.210+411C>T		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108992 AN: 152008 Hom.: 41312 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.717 AC: 109112 AN: 152126 Hom.: 41374 Cov.: 32 AF XY: 0.719 AC XY: 53478 AN XY: 74372

African (AFR) AF: 0.927 AC: 38515 AN: 41540

American (AMR) AF: 0.791 AC: 12081 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2563 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.840 AC: 4044 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5023 AN: 10560

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39340 AN: 67958

Other (OTH) AF: 0.743 AC: 1570 AN: 2114

Alfa AF: 0.516 Hom.: 1649

Bravo AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.65
PhyloP100		0.36
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2069833;

hg19: chr7-22767664;