rs7802308

chr7-22726815-T-A

Variant summary

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

The NR_131935.1(IL6-AS1):n.54-110A>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 146,400 control chromosomes in the GnomAD database, including 5,183 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 0.24 (4991 hom., cov: 31)
  • Exomes 𝑓: 0.16 (192 hom.)
• Consequence: IL6-AS1 NR_131935.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979

Genes affected

IL6-AS1 (HGNC:40301): (IL6 antisense RNA 1)

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]

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6-AS1	NR_131935.1	n.54-110A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6-AS1	ENST00000325042.2	n.54-110A>T		intron_variant, non_coding_transcript_variant		1
IL6	ENST00000404625.5	c.-84-364T>A		intron_variant		5		P1
STEAP1B	ENST00000650428.1	n.46+753A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.243 AC: 33716 AN: 138878 Hom.: 4991 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.160 AC: 1184 AN: 7420 Hom.: 192 AF XY: 0.160 AC XY: 612 AN XY: 3818

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.243 AC: 33748 AN: 138980 Hom.: 4991 Cov.: 31 AF XY: 0.252 AC XY: 17134 AN XY: 67972

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.275

Alfa AF: 0.185 Hom.: 340

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.8
Dann	Benign	0.17

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: rs7802308; hg19: chr7-22766434; COSMIC: COSV51732761; COSMIC: COSV51732761;