rs13306433

Positions:

• chr7-22729295-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000258743.10(IL6):​c.325-219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,284 control chromosomes in the GnomAD database, including 97 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 0.019 (97 hom., cov: 32)
• Consequence: IL6 ENST00000258743.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.325-219G>A		intron_variant		ENST00000258743.10	NP_000591.1
IL6	NM_001318095.2	c.97-219G>A		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.256-219G>A		intron_variant			NP_001358025.1
IL6	XM_005249745.6	c.487-219G>A		intron_variant			XP_005249802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.325-219G>A		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2915 AN: 152166 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00982

Gnomad OTH AF: 0.0168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0192 AC: 2924 AN: 152284 Hom.: 97 Cov.: 32 AF XY: 0.0223 AC XY: 1662 AN XY: 74466

Gnomad4 AFR AF: 0.00426

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0285

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.00984

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0135 Hom.: 11

Bravo AF: 0.0230

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.81

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: rs13306433; hg19: chr7-22768914;