7-22727814-A-G

Variant names:

• chr7-22727814-A-G
• rs2069832
• NM_000600.5:c.210+180A>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.210+180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,166 control chromosomes in the GnomAD database, including 41,407 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 0.72 (41407 hom., cov: 32)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 72 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-AS1 (HGNC:40301): (IL6 antisense RNA 1)

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.976 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.210+180A>G		intron	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.141+180A>G		intron	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-19+533A>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.210+180A>G		intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.372+180A>G		intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.210+180A>G		intron	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109049 AN: 152048 Hom.: 41339 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.717 AC: 109175 AN: 152166 Hom.: 41407 Cov.: 32 AF XY: 0.719 AC XY: 53509 AN XY: 74376

African (AFR) AF: 0.927 AC: 38514 AN: 41540

American (AMR) AF: 0.791 AC: 12095 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2563 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5161 AN: 5170

South Asian (SAS) AF: 0.842 AC: 4063 AN: 4828

European-Finnish (FIN) AF: 0.477 AC: 5039 AN: 10564

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39367 AN: 67978

Other (OTH) AF: 0.743 AC: 1568 AN: 2110

Alfa AF: 0.649 Hom.: 51095

Bravo AF: 0.751

Asia WGS AF: 0.920 AC: 3196 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	0.91
DANN	Benign	0.43
PhyloP100		-0.98
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: rs2069832; hg19: chr7-22767433;