rs2069843

Positions:

• chr7-22730375-G-A

Variant summary

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

The ENST00000258743.10(IL6):​c.471+715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 813,056 control chromosomes in the GnomAD database, including 725 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 0.055 (416 hom., cov: 32)
  • Exomes 𝑓: 0.025 (309 hom.)
• Consequence: IL6 ENST00000258743.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.471+715G>A		intron_variant		ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6	c.*589G>A		3_prime_UTR_variant	3/3		XP_005249802.1
IL6	NM_001318095.2	c.243+715G>A		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.402+715G>A		intron_variant			NP_001358025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.471+715G>A		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8352 AN: 152082 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0245 AC: 16205 AN: 660856 Hom.: 309 Cov.: 8 AF XY: 0.0243 AC XY: 7493 AN XY: 307854

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0592

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.000703

Gnomad4 SAS exome AF: 0.0513

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.0550 AC: 8365 AN: 152200 Hom.: 416 Cov.: 32 AF XY: 0.0548 AC XY: 4078 AN XY: 74412

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0567

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0441 Hom.: 42

Bravo AF: 0.0619

Asia WGS AF: 0.0320 AC: 113 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	4.9
DANN	Benign	0.41

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: rs2069843; hg19: chr7-22769994;