7-22728289-C-G

Variant names:

• chr7-22728289-C-G
• rs1474348
• NM_000600.5:c.211-404C>G

Variant summary

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

The NM_000600.5(IL6):​c.211-404C>G 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 152,092 control chromosomes in the GnomAD database, including 41,369 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 (41369 hom., cov: 31)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 36 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.211-404C>G		intron_variant	Intron 2 of 4	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1	c.142-404C>G		intron_variant	Intron 2 of 4		NP_001358025.1
IL6	NM_001318095.2	c.-18-404C>G		intron_variant	Intron 1 of 3		NP_001305024.1
IL6	XM_005249745.6	c.373-404C>G		intron_variant	Intron 1 of 2		XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.211-404C>G		intron_variant	Intron 2 of 4	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108970 AN: 151974 Hom.: 41301 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.477

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: 109096 AN: 152092 Hom.: 41369 Cov.: 31 AF XY: 0.719 AC XY: 53461 AN XY: 74336

African (AFR) AF: 0.927 AC: 38513 AN: 41530

American (AMR) AF: 0.790 AC: 12082 AN: 15286

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

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

South Asian (SAS) AF: 0.839 AC: 4036 AN: 4810

European-Finnish (FIN) AF: 0.477 AC: 5034 AN: 10550

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

European-Non Finnish (NFE) AF: 0.579 AC: 39324 AN: 67948

Other (OTH) AF: 0.742 AC: 1568 AN: 2112

Alfa AF: 0.640 Hom.: 4120

Bravo AF: 0.751

Asia WGS AF: 0.917 AC: 3185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.39
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1474348; hg19: chr7-22767908;