rs2069857

chr7-22727215-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000600.5(IL6):c.-48C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00171 in 1,611,092 control chromosomes in the GnomAD database, including 4 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 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: IL6 NM_000600.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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]

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

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS2: High AC in GnomAd at 234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6	NM_000600.5	c.-48C>A		5_prime_UTR_variant	1/5	ENST00000258743.10
IL6-AS1	NR_131935.1	n.53+353G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6	ENST00000258743.10	c.-48C>A		5_prime_UTR_variant	1/5	1	NM_000600.5	P1
IL6-AS1	ENST00000325042.2	n.53+353G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00185 AC: 464 AN: 250248 Hom.: 3 AF XY: 0.00192 AC XY: 260 AN XY: 135292

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00833

Gnomad NFE exome AF: 0.00214

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00173 AC: 2522 AN: 1458838 Hom.: 4 Cov.: 31 AF XY: 0.00170 AC XY: 1235 AN XY: 725860

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.000583

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000279

Gnomad4 FIN exome AF: 0.00746

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00154 AC: 234 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74460

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00782

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00183 Hom.: 3

Bravo AF: 0.000929

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.80

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: rs2069857; hg19: chr7-22766834;