IL6 p.Leu61Leu

Variant names:

• chr7-22727604-C-C
• ENST00000258743.10:c.

Your query was ambiguous. Multiple possible variants found:

• chr7-22727605--
• chr7-22727607-C-T
• chr7-22727607-C-A
• chr7-22727607-C-G
• chr7-22727605-CTC-TTA
• chr7-22727605-CTC-TTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000258743.10(IL6):​c. variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL6 ENST00000258743.10 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000258743.10. 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-AS1	NR_131935.1		n.		exon_region	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.		splice_donor intron	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6-AS1	ENST00000325042.2	TSL:1	n.		exon_region	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-22767223;