NM_000600.5:c.471+494G>C

Variant names:

• chr7-22730154-G-C
• rs1548216
• NM_000600.5:c.471+494G>C

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+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 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 20 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 (AFR) allele frequency at 95% confidence interval = 0.177 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.471+494G>C		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.402+494G>C		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.243+494G>C		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.471+494G>C		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.633+494G>C		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.471+494G>C		intron	N/A	ENSP00000385675.1	P05231

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

African (AFR) AF: 0.200 AC: 3156 AN: 15784

American (AMR) AF: 0.0630 AC: 62 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0699 AC: 360 AN: 5152

East Asian (EAS) AF: 0.000826 AC: 3 AN: 3630

South Asian (SAS) AF: 0.0522 AC: 859 AN: 16458

European-Finnish (FIN) AF: 0.0181 AC: 5 AN: 276

Middle Eastern (MID) AF: 0.0340 AC: 55 AN: 1620

European-Non Finnish (NFE) AF: 0.0223 AC: 16976 AN: 761894

Other (OTH) AF: 0.0340 AC: 928 AN: 27298

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

African (AFR) AF: 0.180 AC: 7491 AN: 41510

American (AMR) AF: 0.0572 AC: 875 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4826

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1511 AN: 68022

Other (OTH) AF: 0.0577 AC: 122 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.75
PhyloP100		-0.12
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: rs1548216; hg19: chr7-22769773;