7-22732035-C-T

Position:

• chr7-22732035-C-T

Variant summary

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

The 7-22732035-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 145,996 control chromosomes in the GnomAD database, including 313 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 0.057 (311 hom., cov: 30)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: IL6 NM_000600.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5			downstream_gene_variant		ENST00000258743.10
IL6	NM_001318095.2			downstream_gene_variant
IL6	NM_001371096.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10			downstream_gene_variant		1	NM_000600.5	P1
IL6	ENST00000404625.5			downstream_gene_variant		5		P1
IL6	ENST00000407492.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8380 AN: 145938 Hom.: 312 Cov.: 30

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0498

GnomAD4 exome AF: 0.229 AC: 11 AN: 48 Hom.: 2 Cov.: 0 AF XY: 0.214 AC XY: 6 AN XY: 28

Gnomad4 FIN exome AF: 0.229

GnomAD4 genome AF: 0.0574 AC: 8374 AN: 145948 Hom.: 311 Cov.: 30 AF XY: 0.0541 AC XY: 3836 AN XY: 70860

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0495

Alfa AF: 0.0416 Hom.: 31

Bravo AF: 0.0537

Asia WGS AF: 0.0170 AC: 59 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2069861; hg19: chr7-22771654;