rs1474347

chr7-22728505-C-Achr7-22728505-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.211-188C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 568,656 control chromosomes in the GnomAD database, including 131,270 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 0.69 (38089 hom., cov: 32)
  • Exomes 𝑓: 0.65 (93181 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.211-188C>A		intron_variant		ENST00000258743.10
IL6	NM_001318095.2	c.-18-188C>A		intron_variant
IL6	NM_001371096.1	c.142-188C>A		intron_variant
IL6	XM_005249745.6	c.373-188C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.211-188C>A		intron_variant		1	NM_000600.5	P1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105268 AN: 152002 Hom.: 38032 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.652 AC: 271475 AN: 416536 Hom.: 93181 Cov.: 2 AF XY: 0.660 AC XY: 143495 AN XY: 217362

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.740

Gnomad4 EAS exome AF: 0.995

Gnomad4 SAS exome AF: 0.816

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.693 AC: 105383 AN: 152120 Hom.: 38089 Cov.: 32 AF XY: 0.695 AC XY: 51686 AN XY: 74358

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.729

Alfa AF: 0.631 Hom.: 31835

Bravo AF: 0.724

Asia WGS AF: 0.911 AC: 3165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.5
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1474347; hg19: chr7-22768124;