7-22728600-C-T

Variant names:

• chr7-22728600-C-T
• rs1524107
• NM_000600.5:c.211-93C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000600.5(IL6):​c.211-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 753,688 control chromosomes in the GnomAD database, including 17,045 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 0.11 (2349 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14696 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 71 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.211-93C>T		intron_variant	Intron 2 of 4	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1	c.142-93C>T		intron_variant	Intron 2 of 4		NP_001358025.1
IL6	NM_001318095.2	c.-18-93C>T		intron_variant	Intron 1 of 3		NP_001305024.1
IL6	XM_005249745.6	c.373-93C>T		intron_variant	Intron 1 of 2		XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.211-93C>T		intron_variant	Intron 2 of 4	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16101 AN: 152084 Hom.: 2353 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.129 AC: 77493 AN: 601486 Hom.: 14696 Cov.: 8 AF XY: 0.135 AC XY: 43096 AN XY: 319962

African (AFR) AF: 0.0793 AC: 1217 AN: 15348

American (AMR) AF: 0.284 AC: 8721 AN: 30666

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 1541 AN: 18266

East Asian (EAS) AF: 0.762 AC: 24639 AN: 32320

South Asian (SAS) AF: 0.301 AC: 17660 AN: 58672

European-Finnish (FIN) AF: 0.0300 AC: 1446 AN: 48134

Middle Eastern (MID) AF: 0.0885 AC: 357 AN: 4034

European-Non Finnish (NFE) AF: 0.0500 AC: 18139 AN: 362518

Other (OTH) AF: 0.120 AC: 3773 AN: 31528

GnomAD4 genome AF: 0.106 AC: 16121 AN: 152202 Hom.: 2349 Cov.: 32 AF XY: 0.113 AC XY: 8431 AN XY: 74424

African (AFR) AF: 0.0803 AC: 3333 AN: 41526

American (AMR) AF: 0.197 AC: 3008 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3896 AN: 5162

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4822

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3344 AN: 68018

Other (OTH) AF: 0.123 AC: 259 AN: 2114

Alfa AF: 0.0808 Hom.: 2447

Bravo AF: 0.117

Asia WGS AF: 0.489 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.5
DANN	Benign	0.76
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

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: rs1524107; hg19: chr7-22768219;