7-22728408-A-G

Variant names:

• chr7-22728408-A-G
• rs2069837
• NM_000600.5:c.211-285A>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.211-285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 387,012 control chromosomes in the GnomAD database, including 2,046 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 0.096 (809 hom., cov: 32)
  • Exomes 𝑓: 0.091 (1237 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• Publications: 166 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 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.211-285A>G		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.142-285A>G		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-18-285A>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.211-285A>G		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.373-285A>G		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.211-285A>G		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14643 AN: 152094 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0908 AC: 21323 AN: 234800 Hom.: 1237 AF XY: 0.0941 AC XY: 11365 AN XY: 120816

African (AFR) AF: 0.114 AC: 980 AN: 8592

American (AMR) AF: 0.0693 AC: 772 AN: 11148

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 1024 AN: 7792

East Asian (EAS) AF: 0.161 AC: 2709 AN: 16810

South Asian (SAS) AF: 0.150 AC: 3143 AN: 20956

European-Finnish (FIN) AF: 0.0614 AC: 741 AN: 12062

Middle Eastern (MID) AF: 0.150 AC: 164 AN: 1094

European-Non Finnish (NFE) AF: 0.0734 AC: 10425 AN: 141942

Other (OTH) AF: 0.0948 AC: 1365 AN: 14404

GnomAD4 genome AF: 0.0963 AC: 14660 AN: 152212 Hom.: 809 Cov.: 32 AF XY: 0.0980 AC XY: 7294 AN XY: 74420

African (AFR) AF: 0.124 AC: 5150 AN: 41534

American (AMR) AF: 0.0865 AC: 1324 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3466

East Asian (EAS) AF: 0.170 AC: 881 AN: 5180

South Asian (SAS) AF: 0.162 AC: 782 AN: 4814

European-Finnish (FIN) AF: 0.0648 AC: 686 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4995 AN: 68012

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.0819 Hom.: 1975

Bravo AF: 0.0978

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.84
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: rs2069837; hg19: chr7-22768027;