7-22728408-A-G

Position:

• chr7-22728408-A-G

Variant summary

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

The ENST00000258743.10(IL6):​c.211-285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 387,012 control chromosomes in the GnomAD database, including 2,046 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 0.096 (809 hom., cov: 32)
  • Exomes 𝑓: 0.091 (1237 hom.)
• Consequence: IL6 ENST00000258743.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837

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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.211-285A>G		intron_variant		ENST00000258743.10	NP_000591.1
IL6	NM_001318095.2	c.-18-285A>G		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.142-285A>G		intron_variant			NP_001358025.1
IL6	XM_005249745.6	c.373-285A>G		intron_variant			XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.211-285A>G		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14643 AN: 152094 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0908 AC: 21323 AN: 234800 Hom.: 1237 AF XY: 0.0941 AC XY: 11365 AN XY: 120816

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0693

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0734

Gnomad4 OTH exome AF: 0.0948

GnomAD4 genome AF: 0.0963 AC: 14660 AN: 152212 Hom.: 809 Cov.: 32 AF XY: 0.0980 AC XY: 7294 AN XY: 74420

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0786 Hom.: 834

Bravo AF: 0.0978

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.68

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: rs2069837; hg19: chr7-22768027;