NM_002184.4:c.1841-621A>G

Variant names:

• chr5-55948210-T-C
• rs11574780
• NM_002184.4:c.1841-621A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002184.4(IL6ST):​c.1841-621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,250 control chromosomes in the GnomAD database, including 81 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 0.027 (81 hom., cov: 32)
• Consequence: IL6ST NM_002184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0268 (4080/152250) while in subpopulation NFE AF= 0.0408 (2777/67986). AF 95% confidence interval is 0.0396. There are 81 homozygotes in gnomad4. There are 1931 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 81 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL6ST	NM_002184.4	c.1841-621A>G		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.1841-621A>G		intron_variant	Intron 14 of 16	1	NM_002184.4	ENSP00000370698.2

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4086 AN: 152132 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00868

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0268 AC: 4080 AN: 152250 Hom.: 81 Cov.: 32 AF XY: 0.0259 AC XY: 1931 AN XY: 74458

Gnomad4 AFR AF: 0.00630

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0369 Hom.: 148

Bravo AF: 0.0265

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.83

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: rs11574780; hg19: chr5-55244038;