rs2069851

Positions:

• chr7-22731685-G-A
• chr7-22731685-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000600.5(IL6):​c.*112G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 529,390 control chromosomes in the GnomAD database, including 2 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 0.00087 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: IL6 NM_000600.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS2: High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.*112G>A		3_prime_UTR_variant	5/5	ENST00000258743.10
IL6	NM_001318095.2	c.*112G>A		3_prime_UTR_variant	4/4
IL6	NM_001371096.1	c.*112G>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.*112G>A		3_prime_UTR_variant	5/5	1	NM_000600.5	P1

Frequencies

GnomAD3 genomes AF: 0.000868 AC: 132 AN: 152150 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000159 AC: 60 AN: 377122 Hom.: 1 Cov.: 6 AF XY: 0.000117 AC XY: 22 AN XY: 188000

Gnomad4 AFR exome AF: 0.00333

Gnomad4 AMR exome AF: 0.000392

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000431

Gnomad4 SAS exome AF: 0.000780

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000444

Gnomad4 OTH exome AF: 0.000442

GnomAD4 genome AF: 0.000873 AC: 133 AN: 152268 Hom.: 1 Cov.: 31 AF XY: 0.000833 AC XY: 62 AN XY: 74460

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000527 Hom.: 0

Bravo AF: 0.000850

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.73

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: rs2069851; hg19: chr7-22771304;