rs1800795

Variant names:

• chr7-22727026-C-G
• rs1800795
• ENST00000325042.2:n.54-321G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-22727026-C-G
• chr7-22727026-C-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.54-321G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 554,376 control chromosomes in the GnomAD database, including 131,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.72 (41246 hom., cov: 29)
  • Exomes 𝑓: 0.65 (90392 hom.)
• Consequence: IL6-AS1 ENST00000325042.2 intron
• Clinical Significance: other; risk factor no assertion criteria provided O:7
• Conservation: PhyloP100: 3.25
• Publications: 2714 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6	NM_000600.5	c.-237C>G		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.-237C>G		upstream_gene_variant		1	NM_000600.5	ENSP00000258743.5

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108695 AN: 151800 Hom.: 41177 Cov.: 29

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.738

GnomAD4 exome AF: 0.652 AC: 262377 AN: 402458 Hom.: 90392 AF XY: 0.661 AC XY: 139725 AN XY: 211226

African (AFR) AF: 0.935 AC: 10202 AN: 10910

American (AMR) AF: 0.816 AC: 11884 AN: 14558

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 9148 AN: 12384

East Asian (EAS) AF: 0.999 AC: 27354 AN: 27374

South Asian (SAS) AF: 0.821 AC: 32241 AN: 39258

European-Finnish (FIN) AF: 0.459 AC: 12423 AN: 27070

Middle Eastern (MID) AF: 0.798 AC: 1426 AN: 1788

European-Non Finnish (NFE) AF: 0.577 AC: 141674 AN: 245580

Other (OTH) AF: 0.681 AC: 16025 AN: 23536

GnomAD4 genome AF: 0.716 AC: 108822 AN: 151918 Hom.: 41246 Cov.: 29 AF XY: 0.718 AC XY: 53336 AN XY: 74234

African (AFR) AF: 0.927 AC: 38449 AN: 41456

American (AMR) AF: 0.789 AC: 12057 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2559 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5133 AN: 5142

South Asian (SAS) AF: 0.841 AC: 4038 AN: 4804

European-Finnish (FIN) AF: 0.476 AC: 5009 AN: 10530

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39216 AN: 67930

Other (OTH) AF: 0.740 AC: 1558 AN: 2104

Alfa AF: 0.639 Hom.: 4111

Bravo AF: 0.750

Asia WGS AF: 0.914 AC: 3175 AN: 3478

ClinVar

Significance: other; risk factor

Submissions summary: Other:7

Revision: no assertion criteria provided

Submissions by phenotype

Crohn disease-associated growth failure, susceptibility to Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Diabetes mellitus, type 1, susceptibility to Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Diabetes mellitus type 2, susceptibility to Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

INTRACRANIAL HEMORRHAGE IN BRAIN CEREBROVASCULAR MALFORMATIONS, SUSCEPTIBILITY TO Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Kaposi sarcoma Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Cholangiocarcinoma Other:1

Dec 10, 2022

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Significance: other

Review Status: no assertion criteria provided

Collection Method: research

No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

RHEUMATOID ARTHRITIS, SYSTEMIC JUVENILE, SUSCEPTIBILITY TO Other:1

Sep 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		3.3
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1800795; hg19: chr7-22766645;