rs2069835

Positions:

• chr7-22728252-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.211-441T>C		intron_variant		ENST00000258743.10
IL6	NM_001318095.2	c.-18-441T>C		intron_variant
IL6	NM_001371096.1	c.142-441T>C		intron_variant
IL6	XM_005249745.6	c.373-441T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.211-441T>C		intron_variant		1	NM_000600.5	P1

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

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0674

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0663 Hom.: 252

Bravo AF: 0.0733

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069835; hg19: chr7-22767871;