rs528464156

Variant names:

• chr1-154405680-A-G
• rs528464156
• NM_000565.4:c.51A>G

Variant summary

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

The NM_000565.4(IL6R):​c.51A>G​(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,528,286 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (22 hom.)
• Consequence: IL6R NM_000565.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.722
• Publications: 0 publications found

Genes affected

IL6R (HGNC:6019): (interleukin 6 receptor) This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

IL6R-AS1 (HGNC:53716): (IL6R antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-154405680-A-G is Benign according to our data. Variant chr1-154405680-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1164781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.722 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000565.4. 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
	IL6R	NM_000565.4	MANE Select	c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 10	NP_000556.1	P08887-1
	IL6R	NM_001382769.1		c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 11	NP_001369698.1
	IL6R	NM_001382770.1		c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 11	NP_001369699.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL6R	ENST00000368485.8	TSL:1 MANE Select	c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 10	ENSP00000357470.3	P08887-1
	IL6R	ENST00000344086.8	TSL:1	c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 9	ENSP00000340589.4	P08887-2
	IL6R	ENST00000622330.5	TSL:1	c.51A>G	p.Gly17Gly	synonymous	Exon 1 of 7	ENSP00000477739.1	A0A087WTB5

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152036 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00346

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00348 AC: 430 AN: 123670 AF XY: 0.00321

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.0225

Gnomad EAS exome AF: 0.000103

Gnomad FIN exome AF: 0.000563

Gnomad NFE exome AF: 0.00360

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00396 AC: 5449 AN: 1376136 Hom.: 22 Cov.: 32 AF XY: 0.00383 AC XY: 2603 AN XY: 679126

African (AFR) AF: 0.000493 AC: 15 AN: 30410

American (AMR) AF: 0.00266 AC: 94 AN: 35354

Ashkenazi Jewish (ASJ) AF: 0.0247 AC: 611 AN: 24712

East Asian (EAS) AF: 0.0000859 AC: 3 AN: 34944

South Asian (SAS) AF: 0.000152 AC: 12 AN: 78828

European-Finnish (FIN) AF: 0.000447 AC: 15 AN: 33536

Middle Eastern (MID) AF: 0.000463 AC: 2 AN: 4322

European-Non Finnish (NFE) AF: 0.00414 AC: 4455 AN: 1076618

Other (OTH) AF: 0.00422 AC: 242 AN: 57412

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152150 Hom.: 1 Cov.: 32 AF XY: 0.00259 AC XY: 193 AN XY: 74384

African (AFR) AF: 0.000747 AC: 31 AN: 41514

American (AMR) AF: 0.00379 AC: 58 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10606

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00346 AC: 235 AN: 67980

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00535 Hom.: 1

Bravo AF: 0.00306

Asia WGS AF: 0.000578 AC: 3 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	IL6R-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
DANN	Benign	0.69
PhyloP100		-0.72
PromoterAI		-0.13	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs528464156; hg19: chr1-154378156;