chr1-154405422-G-A

Position:

• chr1-154405422-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.-208G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 533,660 control chromosomes in the GnomAD database, including 40,960 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 0.38 (11390 hom., cov: 34)
  • Exomes 𝑓: 0.39 (29570 hom.)
• Consequence: IL6R NM_000565.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6R	NM_000565.4	c.-208G>A		5_prime_UTR_variant	1/10	ENST00000368485.8	NP_000556.1
IL6R-AS1	NR_147855.1	n.126+1017C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6R	ENST00000368485.8	c.-208G>A		5_prime_UTR_variant	1/10	1	NM_000565.4	ENSP00000357470	P1
IL6R	ENST00000344086.8	c.-208G>A		5_prime_UTR_variant	1/9	1		ENSP00000340589
IL6R	ENST00000622330.5	c.-208G>A		5_prime_UTR_variant	1/7	1		ENSP00000477739
IL6R-AS1	ENST00000424435.1	n.126+1017C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58108 AN: 152056 Hom.: 11382 Cov.: 34

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.391 AC: 149201 AN: 381486 Hom.: 29570 Cov.: 4 AF XY: 0.386 AC XY: 78153 AN XY: 202536

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.382 AC: 58131 AN: 152174 Hom.: 11390 Cov.: 34 AF XY: 0.386 AC XY: 28700 AN XY: 74396

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.359

Alfa AF: 0.386 Hom.: 9169

Bravo AF: 0.381

Asia WGS AF: 0.367 AC: 1275 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4845617; hg19: chr1-154377898;