7-22729088-T-G

Variant names:

• chr7-22729088-T-G
• rs1554606
• NM_000600.5:c.324+282T>G

Variant summary

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

The NM_000600.5(IL6):​c.324+282T>G 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 152,134 control chromosomes in the GnomAD database, including 30,301 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 (30301 hom., cov: 32)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 109 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	NM_000600.5	MANE Select	c.324+282T>G		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.255+282T>G		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.96+282T>G		intron	N/A	NP_001305024.1	B5MC21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.324+282T>G		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.486+282T>G		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.324+282T>G		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94555 AN: 152016 Hom.: 30269 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.622 AC: 94641 AN: 152134 Hom.: 30301 Cov.: 32 AF XY: 0.626 AC XY: 46525 AN XY: 74376

African (AFR) AF: 0.663 AC: 27527 AN: 41490

American (AMR) AF: 0.725 AC: 11097 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5141 AN: 5184

South Asian (SAS) AF: 0.781 AC: 3773 AN: 4828

European-Finnish (FIN) AF: 0.453 AC: 4788 AN: 10568

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

European-Non Finnish (NFE) AF: 0.556 AC: 37792 AN: 67972

Other (OTH) AF: 0.671 AC: 1415 AN: 2108

Alfa AF: 0.584 Hom.: 44954

Bravo AF: 0.645

Asia WGS AF: 0.873 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.77
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: rs1554606; hg19: chr7-22768707;