7-22728630-G-T

Variant names:

• chr7-22728630-G-T
• rs2066992
• NM_000600.5:c.211-63G>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.211-63G>T variant causes a intron change. The variant allele was found at a frequency of 0.12 in 893,316 control chromosomes in the GnomAD database, including 18,824 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 (2351 hom., cov: 32)
  • Exomes 𝑓: 0.12 (16473 hom.)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 93 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=-0.51).
• 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.211-63G>T		intron_variant	Intron 2 of 4	ENST00000258743.10	NP_000591.1
IL6	NM_001371096.1	c.142-63G>T		intron_variant	Intron 2 of 4		NP_001358025.1
IL6	NM_001318095.2	c.-18-63G>T		intron_variant	Intron 1 of 3		NP_001305024.1
IL6	XM_005249745.6	c.373-63G>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.211-63G>T		intron_variant	Intron 2 of 4	1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16107 AN: 152062 Hom.: 2355 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.123 AC: 91030 AN: 741136 Hom.: 16473 Cov.: 10 AF XY: 0.128 AC XY: 50348 AN XY: 393400

African (AFR) AF: 0.0796 AC: 1463 AN: 18380

American (AMR) AF: 0.297 AC: 12169 AN: 41002

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 1800 AN: 21320

East Asian (EAS) AF: 0.762 AC: 25888 AN: 33994

South Asian (SAS) AF: 0.301 AC: 20730 AN: 68874

European-Finnish (FIN) AF: 0.0301 AC: 1570 AN: 52118

Middle Eastern (MID) AF: 0.0894 AC: 393 AN: 4396

European-Non Finnish (NFE) AF: 0.0488 AC: 22687 AN: 464624

Other (OTH) AF: 0.119 AC: 4330 AN: 36428

GnomAD4 genome AF: 0.106 AC: 16127 AN: 152180 Hom.: 2351 Cov.: 32 AF XY: 0.113 AC XY: 8432 AN XY: 74410

African (AFR) AF: 0.0802 AC: 3332 AN: 41522

American (AMR) AF: 0.197 AC: 3013 AN: 15286

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

East Asian (EAS) AF: 0.755 AC: 3902 AN: 5168

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4814

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0492 AC: 3343 AN: 67996

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

Alfa AF: 0.0794 Hom.: 3893

Bravo AF: 0.117

Asia WGS AF: 0.489 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.73
PhyloP100		4.6
Mutation Taster		=92/8	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: rs2066992; hg19: chr7-22768249; COSMIC: COSV51734549; COSMIC: COSV51734549;