7-22727592-A-G

Variant names:

• chr7-22727592-A-G
• rs199925567
• NM_000600.5:c.168A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000600.5(IL6):​c.168A>G​(p.Gln56Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IL6 NM_000600.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.936 with no splicing effect.

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.168A>G	p.Gln56Gln	synonymous	Exon 2 of 5	NP_000591.1	P05231
	IL6	NM_001371096.1		c.99A>G	p.Gln33Gln	synonymous	Exon 2 of 5	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-19+311A>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.168A>G	p.Gln56Gln	synonymous	Exon 2 of 5	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.330A>G	p.Gln110Gln	synonymous	Exon 1 of 4	ENSP00000512964.1	A0A8Q3SJL1
	IL6-AS1	ENST00000325042.2	TSL:1	n.29T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428734 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 707670

African (AFR) AF: 0.00 AC: 0 AN: 32302

American (AMR) AF: 0.00 AC: 0 AN: 39554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 80450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096630

Other (OTH) AF: 0.00 AC: 0 AN: 58868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.38
PhyloP100		-0.94
PromoterAI		0.065	Neutral

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: rs199925567; hg19: chr7-22767211;