rs2069849

Variant names:

• chr7-22731537-C-T
• rs2069849
• NM_000600.5:c.603C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-22731537-C-T
• chr7-22731537-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000600.5(IL6):​c.603C>T​(p.Phe201Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,605,788 control chromosomes in the GnomAD database, including 1,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.060 (540 hom., cov: 31)
  • Exomes 𝑓: 0.030 (1147 hom.)
• Consequence: IL6 NM_000600.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.748
• Publications: 83 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 7-22731537-C-T is Benign according to our data. Variant chr7-22731537-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056054.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.748 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 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.603C>T	p.Phe201Phe	synonymous	Exon 5 of 5	NP_000591.1	P05231
	IL6	NM_001371096.1		c.534C>T	p.Phe178Phe	synonymous	Exon 5 of 5	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.375C>T	p.Phe125Phe	synonymous	Exon 4 of 4	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.603C>T	p.Phe201Phe	synonymous	Exon 5 of 5	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.765C>T	p.Phe255Phe	synonymous	Exon 4 of 4	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.603C>T	p.Phe201Phe	synonymous	Exon 6 of 6	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9134 AN: 152112 Hom.: 539 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0513

GnomAD2 exomes AF: 0.0436 AC: 10870 AN: 249434 AF XY: 0.0409

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0774

Gnomad ASJ exome AF: 0.0718

Gnomad EAS exome AF: 0.00181

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0299 AC: 43489 AN: 1453558 Hom.: 1147 Cov.: 30 AF XY: 0.0299 AC XY: 21616 AN XY: 722728

African (AFR) AF: 0.153 AC: 5099 AN: 33386

American (AMR) AF: 0.0748 AC: 3325 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 1874 AN: 25978

East Asian (EAS) AF: 0.000884 AC: 35 AN: 39600

South Asian (SAS) AF: 0.0549 AC: 4674 AN: 85214

European-Finnish (FIN) AF: 0.0217 AC: 1157 AN: 53244

Middle Eastern (MID) AF: 0.0339 AC: 194 AN: 5724

European-Non Finnish (NFE) AF: 0.0226 AC: 24986 AN: 1105918

Other (OTH) AF: 0.0357 AC: 2145 AN: 60016

GnomAD4 genome AF: 0.0601 AC: 9149 AN: 152230 Hom.: 540 Cov.: 31 AF XY: 0.0594 AC XY: 4424 AN XY: 74444

African (AFR) AF: 0.144 AC: 5965 AN: 41504

American (AMR) AF: 0.0524 AC: 801 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4828

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1500 AN: 68030

Other (OTH) AF: 0.0503 AC: 106 AN: 2108

Alfa AF: 0.0366 Hom.: 330

Bravo AF: 0.0677

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IL6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.8
DANN	Benign	0.59
PhyloP100		0.75
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: rs2069849; hg19: chr7-22771156;