chr7-22726602-A-G

Variant names:

• chr7-22726602-A-G
• rs1800797
• ENST00000325042.2:n.157T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000325042.2(IL6-AS1):​n.157T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 155,214 control chromosomes in the GnomAD database, including 42,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.72 (41897 hom., cov: 31)
  • Exomes 𝑓: 0.59 (569 hom.)
• Consequence: IL6-AS1 ENST00000325042.2 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0330
• Publications: 476 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-22726602-A-G is Benign according to our data. Variant chr7-22726602-A-G is described in ClinVar as Benign. ClinVar VariationId is 14719.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6-AS1	NR_131935.1		n.157T>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6-AS1	ENST00000325042.2	TSL:1	n.157T>C		non_coding_transcript_exon	Exon 2 of 2
	IL6	ENST00000404625.5	TSL:5	c.-85+344A>G		intron	N/A	ENSP00000385675.1
	STEAP1B	ENST00000650428.1		n.46+966T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109794 AN: 151924 Hom.: 41827 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.591 AC: 1874 AN: 3172 Hom.: 569 Cov.: 0 AF XY: 0.592 AC XY: 1003 AN XY: 1694

African (AFR) AF: 0.894 AC: 59 AN: 66

American (AMR) AF: 0.804 AC: 45 AN: 56

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 71 AN: 102

East Asian (EAS) AF: 1.00 AC: 224 AN: 224

South Asian (SAS) AF: 0.875 AC: 14 AN: 16

European-Finnish (FIN) AF: 0.442 AC: 167 AN: 378

Middle Eastern (MID) AF: 0.778 AC: 14 AN: 18

European-Non Finnish (NFE) AF: 0.544 AC: 1169 AN: 2148

Other (OTH) AF: 0.677 AC: 111 AN: 164

GnomAD4 genome AF: 0.723 AC: 109922 AN: 152042 Hom.: 41897 Cov.: 31 AF XY: 0.725 AC XY: 53905 AN XY: 74338

African (AFR) AF: 0.930 AC: 38566 AN: 41490

American (AMR) AF: 0.792 AC: 12093 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2577 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5165 AN: 5174

South Asian (SAS) AF: 0.850 AC: 4091 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5092 AN: 10554

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39924 AN: 67948

Other (OTH) AF: 0.747 AC: 1577 AN: 2112

Alfa AF: 0.647 Hom.: 95077

Bravo AF: 0.756

Asia WGS AF: 0.917 AC: 3186 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

IL6 POLYMORPHISM Benign:1

Mar 01, 2002

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.72
PhyloP100		0.033
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: rs1800797; hg19: chr7-22766221;