1-154451009-G-T

Position:

• chr1-154451009-G-T

Variant summary

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

The NM_000565.4(IL6R):​c.1066+1029G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,228 control chromosomes in the GnomAD database, including 4,771 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 0.23 (4771 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.1066+1029G>T		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.1066+1029G>T		intron_variant		1	NM_000565.4	P1
IL6R	ENST00000344086.8	c.1066+1029G>T		intron_variant		1
IL6R	ENST00000515190.1	c.474+1029G>T		intron_variant		2
IL6R	ENST00000507256.1	n.264+1029G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34712 AN: 152110 Hom.: 4740 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.229 AC: 34793 AN: 152228 Hom.: 4771 Cov.: 32 AF XY: 0.226 AC XY: 16828 AN XY: 74426

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.216

Alfa AF: 0.171 Hom.: 716

Bravo AF: 0.231

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4845626; hg19: chr1-154423485;