rs4601580

Variant names:

• chr1-154421941-T-A
• rs4601580
• NM_000565.4:c.86-7255T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-154421941-T-A
• chr1-154421941-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000565.4(IL6R):​c.86-7255T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 150,552 control chromosomes in the GnomAD database, including 20,906 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 0.52 (20906 hom., cov: 28)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 21 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 Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 5, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.86-7255T>A		intron_variant	Intron 1 of 9	ENST00000368485.8	NP_000556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.86-7255T>A		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3
IL6R	ENST00000344086.8	c.86-7255T>A		intron_variant	Intron 1 of 8	1		ENSP00000340589.4
IL6R	ENST00000622330.5	c.86-7255T>A		intron_variant	Intron 1 of 6	1		ENSP00000477739.1
IL6R	ENST00000512471.1	c.86-7255T>A		intron_variant	Intron 1 of 3	4		ENSP00000423184.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 78805 AN: 150434 Hom.: 20903 Cov.: 28

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.524 AC: 78845 AN: 150552 Hom.: 20906 Cov.: 28 AF XY: 0.523 AC XY: 38470 AN XY: 73510

African (AFR) AF: 0.447 AC: 18283 AN: 40882

American (AMR) AF: 0.616 AC: 9347 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2072 AN: 3450

East Asian (EAS) AF: 0.516 AC: 2619 AN: 5074

South Asian (SAS) AF: 0.544 AC: 2581 AN: 4746

European-Finnish (FIN) AF: 0.480 AC: 4964 AN: 10348

Middle Eastern (MID) AF: 0.619 AC: 177 AN: 286

European-Non Finnish (NFE) AF: 0.550 AC: 37200 AN: 67604

Other (OTH) AF: 0.526 AC: 1097 AN: 2084

Alfa AF: 0.512 Hom.: 2453

Bravo AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs4601580; hg19: chr1-154394417;