rs2069842

Positions:

• chr7-22729691-G-A
• chr7-22729691-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000600.5(IL6):​c.471+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,614,056 control chromosomes in the GnomAD database, including 240 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 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (116 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017405152).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.471+31G>A		intron_variant		ENST00000258743.10
IL6	XM_005249745.6	c.664G>A	p.Val222Met	missense_variant	3/3
IL6	NM_001318095.2	c.243+31G>A		intron_variant
IL6	NM_001371096.1	c.402+31G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.471+31G>A		intron_variant		1	NM_000600.5	P1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3336 AN: 152192 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.00618 AC: 1552 AN: 251248 Hom.: 47 AF XY: 0.00434 AC XY: 589 AN XY: 135828

Gnomad AFR exome AF: 0.0800

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00240 AC: 3504 AN: 1461746 Hom.: 116 Cov.: 33 AF XY: 0.00208 AC XY: 1511 AN XY: 727172

Gnomad4 AFR exome AF: 0.0791

Gnomad4 AMR exome AF: 0.00492

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000185

Gnomad4 OTH exome AF: 0.00568

GnomAD4 genome AF: 0.0219 AC: 3334 AN: 152310 Hom.: 124 Cov.: 32 AF XY: 0.0213 AC XY: 1583 AN XY: 74482

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0116 Hom.: 29

Bravo AF: 0.0251

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0713 AC: 314

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00737 AC: 895

Asia WGS AF: 0.00606 AC: 22 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.52
DANN	Benign	0.54
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.53	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.027
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.0060	.;B
Vest4		0.13
MVP		0.36
ClinPred		0.0078	T
GERP RS		-5.3

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

LitVar

Other links and lift over

dbSNP: rs2069842; hg19: chr7-22769310;