7-22730530-G-A

Variant names:

• chr7-22730530-G-A
• rs2069845
• NM_000600.5:c.471+870G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000600.5(IL6):​c.471+870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,910 control chromosomes in the GnomAD database, including 30,229 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 0.62 (30229 hom., cov: 31)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 106 publications found

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]

IL6 Gene-Disease associations (from GenCC):

• Kaposi sarcoma, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000600.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	NM_000600.5	MANE Select	c.471+870G>A		intron	N/A	NP_000591.1
	IL6	NM_001371096.1		c.402+870G>A		intron	N/A	NP_001358025.1
	IL6	NM_001318095.2		c.243+870G>A		intron	N/A	NP_001305024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.471+870G>A		intron	N/A	ENSP00000258743.5
	IL6	ENST00000485300.1	TSL:1	c.633+870G>A		intron	N/A	ENSP00000512964.1
	IL6	ENST00000464710.2	TSL:4	n.2647G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94392 AN: 151792 Hom.: 30197 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.668

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94478 AN: 151910 Hom.: 30229 Cov.: 31 AF XY: 0.626 AC XY: 46463 AN XY: 74270

African (AFR) AF: 0.664 AC: 27467 AN: 41390

American (AMR) AF: 0.725 AC: 11067 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2316 AN: 3470

East Asian (EAS) AF: 0.988 AC: 5118 AN: 5180

South Asian (SAS) AF: 0.778 AC: 3746 AN: 4812

European-Finnish (FIN) AF: 0.454 AC: 4792 AN: 10546

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37770 AN: 67936

Other (OTH) AF: 0.672 AC: 1414 AN: 2104

Alfa AF: 0.588 Hom.: 11586

Bravo AF: 0.644

Asia WGS AF: 0.869 AC: 3019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.46
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2069845; hg19: chr7-22770149;