rs2069840

Variant names:

• chr7-22728953-C-G
• rs2069840
• NM_000600.5:c.324+147C>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.324+147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 631,248 control chromosomes in the GnomAD database, including 28,463 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 0.27 (6315 hom., cov: 33)
  • Exomes 𝑓: 0.29 (22148 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 142 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.324+147C>G		intron_variant	Intron 3 of 4	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1	c.255+147C>G		intron_variant	Intron 3 of 4		NP_001358025.1
IL6	NM_001318095.2	c.96+147C>G		intron_variant	Intron 2 of 3		NP_001305024.1
IL6	XM_005249745.6	c.486+147C>G		intron_variant	Intron 2 of 2		XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.324+147C>G		intron_variant	Intron 3 of 4	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41529 AN: 152042 Hom.: 6317 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.290 AC: 138704 AN: 479088 Hom.: 22148 AF XY: 0.286 AC XY: 72511 AN XY: 253444

African (AFR) AF: 0.167 AC: 2196 AN: 13152

American (AMR) AF: 0.340 AC: 7792 AN: 22940

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 3689 AN: 14772

East Asian (EAS) AF: 0.0675 AC: 2116 AN: 31364

South Asian (SAS) AF: 0.191 AC: 9230 AN: 48208

European-Finnish (FIN) AF: 0.241 AC: 9435 AN: 39188

Middle Eastern (MID) AF: 0.217 AC: 793 AN: 3656

European-Non Finnish (NFE) AF: 0.343 AC: 95561 AN: 278730

Other (OTH) AF: 0.291 AC: 7892 AN: 27078

GnomAD4 genome AF: 0.273 AC: 41526 AN: 152160 Hom.: 6315 Cov.: 33 AF XY: 0.268 AC XY: 19915 AN XY: 74406

African (AFR) AF: 0.166 AC: 6879 AN: 41516

American (AMR) AF: 0.344 AC: 5258 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3472

East Asian (EAS) AF: 0.0648 AC: 336 AN: 5184

South Asian (SAS) AF: 0.174 AC: 837 AN: 4820

European-Finnish (FIN) AF: 0.234 AC: 2475 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23931 AN: 67978

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.307 Hom.: 1038

Bravo AF: 0.277

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.51
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: rs2069840; hg19: chr7-22768572; COSMIC: COSV51733989; COSMIC: COSV51733989;