rs13447445

Variant names:

• chr7-22727137-C-A
• rs13447445
• ENST00000325042.2:n.53+431G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-22727137-C-A
• chr7-22727137-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000325042.2(IL6-AS1):​n.53+431G>T variant causes a intron change. The variant allele was found at a frequency of 0.00000113 in 883,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: IL6-AS1 ENST00000325042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.-126C>A		upstream_gene_variant		ENST00000258743.10	NP_000591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.-126C>A		upstream_gene_variant		1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 883120 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 449504

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20726

American (AMR) AF: 0.0000385 AC: 1 AN: 25946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17420

East Asian (EAS) AF: 0.00 AC: 0 AN: 35448

South Asian (SAS) AF: 0.00 AC: 0 AN: 59082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2882

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 634242

Other (OTH) AF: 0.00 AC: 0 AN: 40426

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.89
PhyloP100		3.9
PromoterAI		-0.063	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13447445; hg19: chr7-22766756;