rs2069860

Variant names:

• chr7-22731419-A-G
• NM_000600.5:c.485A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-22731419-A-G
• chr7-22731419-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000600.5(IL6):​c.485A>G​(p.Asp162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D162E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IL6 NM_000600.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068418175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.485A>G	p.Asp162Gly	missense_variant	Exon 5 of 5	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1	c.416A>G	p.Asp139Gly	missense_variant	Exon 5 of 5		NP_001358025.1
IL6	NM_001318095.2	c.257A>G	p.Asp86Gly	missense_variant	Exon 4 of 4		NP_001305024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.485A>G	p.Asp162Gly	missense_variant	Exon 5 of 5	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421590 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 704378

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.7
DANN	Benign	0.45
DEOGEN2	Benign	0.17	T;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.61	.;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;N;N
REVEL	Benign	0.023
Sift	Benign	0.17	T;T;T;T
Sift4G	Uncertain	0.038	D;D;T;D
Polyphen		0.0020	B;B;.;.
Vest4		0.059
MutPred		0.25		Gain of MoRF binding (P = 0.0551);Gain of MoRF binding (P = 0.0551);.;.;
MVP		0.17
MPC		0.23
ClinPred		0.033	T
GERP RS		0.44
Varity_R		0.45
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-22771038;