7-22728630-G-T

Variant summary

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

The NM_000600.5(IL6):c.211-63G>T variant causes a intron change. The variant allele was found at a frequency of 0.12 in 893,316 control chromosomes in the GnomAD database, including 18,824 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 0.11 (2351 hom., cov: 32)
  • Exomes 𝑓: 0.12 (16473 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65

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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.211-63G>T		intron_variant		ENST00000258743.10
IL6	NM_001318095.2	c.-18-63G>T		intron_variant
IL6	NM_001371096.1	c.142-63G>T		intron_variant
IL6	XM_005249745.6	c.373-63G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.211-63G>T		intron_variant		1	NM_000600.5	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16107 AN: 152062 Hom.: 2355 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.123 AC: 91030 AN: 741136 Hom.: 16473 Cov.: 10 AF XY: 0.128 AC XY: 50348 AN XY: 393400

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0844

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.106 AC: 16127 AN: 152180 Hom.: 2351 Cov.: 32 AF XY: 0.113 AC XY: 8432 AN XY: 74410

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.0259

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0768 Hom.: 1208

Bravo AF: 0.117

Asia WGS AF: 0.489 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	20
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: rs2066992; hg19: chr7-22768249; COSMIC: COSV51734549; COSMIC: COSV51734549;