rs1548216

Positions:

• chr7-22730154-G-C

Variant summary

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

The ENST00000258743.10(IL6):​c.471+494G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 985,330 control chromosomes in the GnomAD database, including 1,366 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 0.071 (791 hom., cov: 32)
  • Exomes 𝑓: 0.027 (575 hom.)
• Consequence: IL6 ENST00000258743.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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 (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.471+494G>C		intron_variant		ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6	c.*368G>C		3_prime_UTR_variant	3/3		XP_005249802.1
IL6	NM_001318095.2	c.243+494G>C		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.402+494G>C		intron_variant			NP_001358025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.471+494G>C		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10739 AN: 152116 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0587

GnomAD4 exome AF: 0.0269 AC: 22404 AN: 833096 Hom.: 575 Cov.: 32 AF XY: 0.0264 AC XY: 10161 AN XY: 384702

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0630

Gnomad4 ASJ exome AF: 0.0699

Gnomad4 EAS exome AF: 0.000826

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.0181

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0340

GnomAD4 genome AF: 0.0707 AC: 10768 AN: 152234 Hom.: 791 Cov.: 32 AF XY: 0.0696 AC XY: 5182 AN XY: 74442

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0506 Hom.: 61

Bravo AF: 0.0796

Asia WGS AF: 0.0390 AC: 137 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	7.1
DANN	Benign	0.75

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: rs1548216; hg19: chr7-22769773;