7-22731677-G-A

Variant names:

• chr7-22731677-G-A
• rs13306436
• NM_000600.5:c.*104G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000600.5(IL6):​c.*104G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 649,566 control chromosomes in the GnomAD database, including 22 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 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (22 hom.)
• Consequence: IL6 NM_000600.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 5 publications found

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]

IL6 Gene-Disease associations (from GenCC):

• Kaposi sarcoma, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00112 (171/152302) while in subpopulation EAS AF = 0.0264 (137/5190). AF 95% confidence interval is 0.0228. There are 0 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 171 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000600.5. 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	NM_000600.5	MANE Select	c.*104G>A		3_prime_UTR	Exon 5 of 5	NP_000591.1
	IL6	NM_001371096.1		c.*104G>A		3_prime_UTR	Exon 5 of 5	NP_001358025.1
	IL6	NM_001318095.2		c.*104G>A		3_prime_UTR	Exon 4 of 4	NP_001305024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.*104G>A		3_prime_UTR	Exon 5 of 5	ENSP00000258743.5
	IL6	ENST00000485300.1	TSL:1	c.*104G>A		3_prime_UTR	Exon 4 of 4	ENSP00000512964.1
	IL6	ENST00000404625.5	TSL:5	c.*104G>A		3_prime_UTR	Exon 6 of 6	ENSP00000385675.1

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00242 AC: 1204 AN: 497264 Hom.: 22 Cov.: 7 AF XY: 0.00235 AC XY: 580 AN XY: 246430

African (AFR) AF: 0.00 AC: 0 AN: 12106

American (AMR) AF: 0.000215 AC: 2 AN: 9300

Ashkenazi Jewish (ASJ) AF: 0.00583 AC: 66 AN: 11322

East Asian (EAS) AF: 0.0406 AC: 1020 AN: 25106

South Asian (SAS) AF: 0.000983 AC: 10 AN: 10176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33204

Middle Eastern (MID) AF: 0.000491 AC: 1 AN: 2036

European-Non Finnish (NFE) AF: 0.000146 AC: 54 AN: 369494

Other (OTH) AF: 0.00208 AC: 51 AN: 24520

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.00132 AC XY: 98 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5190

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000429 Hom.: 1

Bravo AF: 0.00157

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs13306436; hg19: chr7-22771296;