7-22726602-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NR_131935.1(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 NR_131935.1 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0330

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6-AS1	NR_131935.1	n.157T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6-AS1	ENST00000325042.2	n.157T>C		non_coding_transcript_exon_variant	2/2	1
IL6	ENST00000404625.5	c.-85+344A>G		intron_variant		5		P1
STEAP1B	ENST00000650428.1	n.46+966T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.677

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

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.747

Alfa AF: 0.637 Hom.: 35553

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

INTERLEUKIN 6 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 01, 2002

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.0
Dann	Benign	0.72

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: rs1800797; hg19: chr7-22766221;