chr1-154422649-G-A

Position:

• chr1-154422649-G-A

Variant summary

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

The NM_000565.4(IL6R):​c.86-6547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,026 control chromosomes in the GnomAD database, including 26,211 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 0.58 (26211 hom., cov: 32)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL6R	NM_000565.4	c.86-6547G>A		intron_variant		ENST00000368485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL6R	ENST00000368485.8	c.86-6547G>A		intron_variant		1	NM_000565.4	P1
IL6R	ENST00000344086.8	c.86-6547G>A		intron_variant		1
IL6R	ENST00000622330.5	c.86-6547G>A		intron_variant		1
IL6R	ENST00000512471.1	c.86-6547G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88753 AN: 151908 Hom.: 26174 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.584 AC: 88845 AN: 152026 Hom.: 26211 Cov.: 32 AF XY: 0.577 AC XY: 42857 AN XY: 74328

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.576

Alfa AF: 0.577 Hom.: 3158

Bravo AF: 0.605

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.49

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: rs11265611; hg19: chr1-154395125;