7-22725837-G-T

Position:

• chr7-22725837-G-T

Variant summary

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

The ENST00000325042.2(IL6-AS1):​n.922C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,212 control chromosomes in the GnomAD database, including 653 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 0.073 (653 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL6-AS1 ENST00000325042.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

Genes affected

IL6-AS1 (HGNC:):

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6-AS1	NR_131935.1	n.922C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6-AS1	ENST00000325042.2	n.922C>A		non_coding_transcript_exon_variant	2/2	1
STEAP1B	ENST00000650428.1	n.46+1731C>A		intron_variant
IL6	ENST00000404625.5	c.-506G>T		upstream_gene_variant		5		ENSP00000385675.1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11036 AN: 152094 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0531

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0725 AC: 11037 AN: 152212 Hom.: 653 Cov.: 32 AF XY: 0.0770 AC XY: 5729 AN XY: 74410

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0432

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.0966

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0763 Hom.: 519

Bravo AF: 0.0554

Asia WGS AF: 0.0150 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069827; hg19: chr7-22765456;