7-22727607-C-T

Variant names:

• chr7-22727607-C-T
• rs140764737
• NM_000600.5:c.183C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000600.5(IL6):​c.183C>T​(p.Leu61Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,565,406 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: IL6 NM_000600.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0560
• Publications: 9 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-AS1 (HGNC:40301): (IL6 antisense RNA 1)

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-22727607-C-T is Benign according to our data. Variant chr7-22727607-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.056 with no splicing effect.
• BS2: High AC in GnomAd4 at 112 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	NM_000600.5	MANE Select	c.183C>T	p.Leu61Leu	synonymous	Exon 2 of 5	NP_000591.1	P05231
	IL6	NM_001371096.1		c.114C>T	p.Leu38Leu	synonymous	Exon 2 of 5	NP_001358025.1	B5MCZ3
	IL6	NM_001318095.2		c.-19+326C>T		intron	N/A	NP_001305024.1	B5MC21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6	ENST00000258743.10	TSL:1 MANE Select	c.183C>T	p.Leu61Leu	synonymous	Exon 2 of 5	ENSP00000258743.5	P05231
	IL6	ENST00000485300.1	TSL:1	c.345C>T	p.Leu115Leu	synonymous	Exon 1 of 4	ENSP00000512964.1	A0A8Q3SJL1
	IL6-AS1	ENST00000325042.2	TSL:1	n.14G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00111 AC: 229 AN: 205992 AF XY: 0.00124

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.000524

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00211

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00269

GnomAD4 exome AF: 0.00120 AC: 1695 AN: 1413090 Hom.: 1 Cov.: 31 AF XY: 0.00118 AC XY: 820 AN XY: 697622

African (AFR) AF: 0.000219 AC: 7 AN: 31976

American (AMR) AF: 0.000365 AC: 14 AN: 38328

Ashkenazi Jewish (ASJ) AF: 0.000844 AC: 19 AN: 22500

East Asian (EAS) AF: 0.00 AC: 0 AN: 39340

South Asian (SAS) AF: 0.0000259 AC: 2 AN: 77316

European-Finnish (FIN) AF: 0.00258 AC: 133 AN: 51646

Middle Eastern (MID) AF: 0.000365 AC: 2 AN: 5484

European-Non Finnish (NFE) AF: 0.00132 AC: 1438 AN: 1088276

Other (OTH) AF: 0.00137 AC: 80 AN: 58224

GnomAD4 genome AF: 0.000735 AC: 112 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74470

African (AFR) AF: 0.0000962 AC: 4 AN: 41584

American (AMR) AF: 0.000262 AC: 4 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000973 Hom.: 1

Bravo AF: 0.000759

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		-0.056
PromoterAI		-0.041	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs140764737; hg19: chr7-22767226; COSMIC: COSV51733811; COSMIC: COSV51733811;