rs2069840

Positions:

• chr7-22728953-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.64).
• 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/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.324+147C>G		intron_variant		ENST00000258743.10	NP_000591.1
IL6	NM_001318095.2	c.96+147C>G		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.255+147C>G		intron_variant			NP_001358025.1
IL6	XM_005249745.6	c.486+147C>G		intron_variant			XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.324+147C>G		intron_variant		1	NM_000600.5	ENSP00000258743	P1

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0675

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.291

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.277

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

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: rs2069840; hg19: chr7-22768572; COSMIC: COSV51733989; COSMIC: COSV51733989;