rs1308837940

Variant names:

• chr1-154405733-C-T
• rs1308837940
• NM_000565.4:c.85+19C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000565.4(IL6R):​c.85+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000538 in 1,301,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: IL6R NM_000565.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.633
• Publications: 0 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-AS1 (HGNC:53716): (IL6R antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-154405733-C-T is Benign according to our data. Variant chr1-154405733-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2972597.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6R	NM_000565.4	c.85+19C>T		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.85+19C>T		intron_variant	Intron 1 of 9	1	NM_000565.4	ENSP00000357470.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000538 AC: 7 AN: 1301314 Hom.: 0 Cov.: 29 AF XY: 0.00000470 AC XY: 3 AN XY: 638688

African (AFR) AF: 0.00 AC: 0 AN: 26150

American (AMR) AF: 0.00 AC: 0 AN: 22094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20328

East Asian (EAS) AF: 0.00 AC: 0 AN: 32010

South Asian (SAS) AF: 0.00 AC: 0 AN: 68436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00000672 AC: 7 AN: 1042360

Other (OTH) AF: 0.00 AC: 0 AN: 54022

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 06, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		0.63
PromoterAI		0.28	Neutral

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: rs1308837940; hg19: chr1-154378209;