chr5-55948949-A-T

Variant names:

• chr5-55948949-A-T
• rs7719246
• ENST00000423954.3:n.77T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000423954.3(IL6ST):​n.77T>A variant causes a non coding transcript exon 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 ENST00000423954.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.119
• Publications: 5 publications found

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]

IL6ST Gene-Disease associations (from GenCC):

• hyper-IgE recurrent infection syndrome 4A, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hyper-IgE recurrent infection syndrome 4, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.1841-1360T>A		intron_variant	Intron 14 of 16	ENST00000381298.7	NP_002175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL6ST	ENST00000381298.7	c.1841-1360T>A		intron_variant	Intron 14 of 16	1	NM_002184.4	ENSP00000370698.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.531 AC: 21995 AN: 41406

American (AMR) AF: 0.152 AC: 2325 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3468

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5184

South Asian (SAS) AF: 0.0747 AC: 361 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1478 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9241 AN: 67996

Other (OTH) AF: 0.219 AC: 462 AN: 2110

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7719246; hg19: chr5-55244777;