rs4329505

chr1-154459944-T-C

Variant summary

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

The NM_000565.4(IL6R):c.1161-5190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,966 control chromosomes in the GnomAD database, including 4,212 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 0.21 (4212 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.1161-5190T>C		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.1161-5190T>C		intron_variant		1	NM_000565.4	P1
IL6R	ENST00000344086.8	c.1067-5190T>C		intron_variant		1
IL6R	ENST00000502679.1	n.474-5190T>C		intron_variant, non_coding_transcript_variant		2
IL6R	ENST00000507256.1	n.359-5190T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32500 AN: 151848 Hom.: 4188 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.214 AC: 32565 AN: 151966 Hom.: 4212 Cov.: 32 AF XY: 0.211 AC XY: 15693 AN XY: 74294

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.185

Alfa AF: 0.172 Hom.: 2501

Bravo AF: 0.217

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.44

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: rs4329505; hg19: chr1-154432420;