rs1474347

Variant names:

• chr7-22728505-C-A
• rs1474347
• NM_000600.5:c.211-188C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-22728505-C-A
• chr7-22728505-C-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.211-188C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 568,656 control chromosomes in the GnomAD database, including 131,270 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 0.69 (38089 hom., cov: 32)
  • Exomes 𝑓: 0.65 (93181 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 60 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 = 0.97 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.211-188C>A		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.142-188C>A		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-18-188C>A		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.211-188C>A		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.373-188C>A		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.211-188C>A		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105268 AN: 152002 Hom.: 38032 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.652 AC: 271475 AN: 416536 Hom.: 93181 Cov.: 2 AF XY: 0.660 AC XY: 143495 AN XY: 217362

African (AFR) AF: 0.853 AC: 10285 AN: 12064

American (AMR) AF: 0.818 AC: 14787 AN: 18082

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 9611 AN: 12990

East Asian (EAS) AF: 0.995 AC: 30142 AN: 30290

South Asian (SAS) AF: 0.816 AC: 30504 AN: 37388

European-Finnish (FIN) AF: 0.458 AC: 13636 AN: 29804

Middle Eastern (MID) AF: 0.789 AC: 1545 AN: 1958

European-Non Finnish (NFE) AF: 0.579 AC: 144369 AN: 249444

Other (OTH) AF: 0.677 AC: 16596 AN: 24516

GnomAD4 genome AF: 0.693 AC: 105383 AN: 152120 Hom.: 38089 Cov.: 32 AF XY: 0.695 AC XY: 51686 AN XY: 74358

African (AFR) AF: 0.844 AC: 35050 AN: 41536

American (AMR) AF: 0.782 AC: 11962 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2562 AN: 3472

East Asian (EAS) AF: 0.993 AC: 5150 AN: 5186

South Asian (SAS) AF: 0.838 AC: 4032 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 4996 AN: 10540

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39291 AN: 67968

Other (OTH) AF: 0.729 AC: 1537 AN: 2108

Alfa AF: 0.639 Hom.: 51784

Bravo AF: 0.724

Asia WGS AF: 0.911 AC: 3165 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	5.5
DANN	Benign	0.68
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1474347; hg19: chr7-22768124;