rs2069844

Positions:

• chr7-22730391-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000600.5(IL6):​c.471+731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 536,224 control chromosomes in the GnomAD database, including 1,810 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 0.089 (1373 hom., cov: 32)
  • Exomes 𝑓: 0.031 (437 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.471+731C>A		intron_variant		ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6	c.*605C>A		3_prime_UTR_variant	3/3		XP_005249802.1
IL6	NM_001371096.1	c.402+731C>A		intron_variant			NP_001358025.1
IL6	NM_001318095.2	c.243+731C>A		intron_variant			NP_001305024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.471+731C>A		intron_variant		1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13482 AN: 152054 Hom.: 1367 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0699

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0699

GnomAD4 exome AF: 0.0305 AC: 11724 AN: 384052 Hom.: 437 Cov.: 5 AF XY: 0.0301 AC XY: 5447 AN XY: 180694

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.0700

Gnomad4 ASJ exome AF: 0.0762

Gnomad4 EAS exome AF: 0.000618

Gnomad4 SAS exome AF: 0.0595

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0414

GnomAD4 genome AF: 0.0888 AC: 13520 AN: 152172 Hom.: 1373 Cov.: 32 AF XY: 0.0875 AC XY: 6511 AN XY: 74400

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.0699

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0483 Hom.: 168

Bravo AF: 0.100

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.46

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: rs2069844; hg19: chr7-22770010;