7-22730530-G-A

Position:

• chr7-22730530-G-A

Variant summary

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

The NM_000600.5(IL6):​c.471+870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,910 control chromosomes in the GnomAD database, including 30,229 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 0.62 (30229 hom., cov: 31)
• Consequence: IL6 NM_000600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6	NM_000600.5	c.471+870G>A		intron_variant		ENST00000258743.10	NP_000591.1
IL6	XM_005249745.6	c.*744G>A		3_prime_UTR_variant	3/3		XP_005249802.1
IL6	NM_001318095.2	c.243+870G>A		intron_variant			NP_001305024.1
IL6	NM_001371096.1	c.402+870G>A		intron_variant			NP_001358025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6	ENST00000258743.10	c.471+870G>A		intron_variant		1	NM_000600.5	ENSP00000258743	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94392 AN: 151792 Hom.: 30197 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.622 AC: 94478 AN: 151910 Hom.: 30229 Cov.: 31 AF XY: 0.626 AC XY: 46463 AN XY: 74270

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.672

Alfa AF: 0.590 Hom.: 4104

Bravo AF: 0.644

Asia WGS AF: 0.869 AC: 3019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.46

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: rs2069845; hg19: chr7-22770149;