7-22731419-AT-TA

Variant names:

• chr7-22731419-AT-TA
• NM_000600.5:c.485_486delATinsTA
• IL6 p.Asp162Val

Variant summary

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

The NM_000600.5(IL6):​c.485_486delATinsTA​(p.Asp162Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: IL6 NM_000600.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• 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 Gene-Disease associations (from GenCC):

• Kaposi sarcoma, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.485_486delATinsTA	p.Asp162Val	missense	N/A	NP_000591.1	P05231
	IL6	NM_001371096.1		c.416_417delATinsTA	p.Asp139Val	missense	N/A	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.257_258delATinsTA	p.Asp86Val	missense	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.485_486delATinsTA	p.Asp162Val	missense	N/A	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.647_648delATinsTA	p.Asp216Val	missense	N/A	ENSP00000512964.1	A0A8Q3SJL1
	IL6	ENST00000404625.5	TSL:5	c.485_486delATinsTA	p.Asp162Val	missense	N/A	ENSP00000385675.1	P05231

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19

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: chr7-22771038;