rs7802308

Variant names:

• chr7-22726815-T-A
• rs7802308
• ENST00000325042.2:n.54-110A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000325042.2(IL6-AS1):​n.54-110A>T variant causes a intron 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 ENST00000325042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000325042.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6-AS1	NR_131935.1		n.54-110A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6-AS1	ENST00000325042.2	TSL:1	n.54-110A>T		intron	N/A
	IL6	ENST00000404625.5	TSL:5	c.-84-364T>A		intron	N/A	ENSP00000385675.1	P05231
	STEAP1B	ENST00000650428.1		n.46+753A>T		intron	N/A

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

African (AFR) AF: 0.303 AC: 54 AN: 178

American (AMR) AF: 0.259 AC: 154 AN: 594

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 41 AN: 218

East Asian (EAS) AF: 0.759 AC: 173 AN: 228

South Asian (SAS) AF: 0.402 AC: 90 AN: 224

European-Finnish (FIN) AF: 0.107 AC: 34 AN: 318

Middle Eastern (MID) AF: 0.214 AC: 6 AN: 28

European-Non Finnish (NFE) AF: 0.107 AC: 560 AN: 5220

Other (OTH) AF: 0.175 AC: 72 AN: 412

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

African (AFR) AF: 0.296 AC: 10638 AN: 35980

American (AMR) AF: 0.311 AC: 4440 AN: 14278

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 942 AN: 3326

East Asian (EAS) AF: 0.789 AC: 3981 AN: 5048

South Asian (SAS) AF: 0.468 AC: 2110 AN: 4510

European-Finnish (FIN) AF: 0.163 AC: 1618 AN: 9902

Middle Eastern (MID) AF: 0.403 AC: 108 AN: 268

European-Non Finnish (NFE) AF: 0.146 AC: 9161 AN: 62878

Other (OTH) AF: 0.275 AC: 537 AN: 1950

Alfa AF: 0.185 Hom.: 340

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.17
PhyloP100		0.98
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	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: rs7802308; hg19: chr7-22766434; COSMIC: COSV51732761; COSMIC: COSV51732761;