rs7719246

Positions:

• chr5-55948949-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002184.4(IL6ST):​c.1841-1360T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,062 control chromosomes in the GnomAD database, including 7,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (7007 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: IL6ST NM_002184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.119

Genes affected

IL6ST (HGNC:6021): (interleukin 6 cytokine family signal transducer) The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 5-55948949-A-T is Benign according to our data. Variant chr5-55948949-A-T is described in ClinVar as [Benign]. Clinvar id is 2688474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.1841-1360T>A		intron_variant		ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7	c.1841-1360T>A		intron_variant		1	NM_002184.4	ENSP00000370698	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36703 AN: 151940 Hom.: 6985 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.242 AC: 36780 AN: 152058 Hom.: 7007 Cov.: 32 AF XY: 0.234 AC XY: 17432 AN XY: 74352

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.219

Alfa AF: 0.191 Hom.: 588

Bravo AF: 0.258

Asia WGS AF: 0.105 AC: 368 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7719246; hg19: chr5-55244777;