chr19-55364706-G-C

Variant names:

• chr19-55364706-G-C
• rs1126760
• NM_000641.4:c.*1301C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000641.4(IL11):​c.*1301C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 152,010 control chromosomes in the GnomAD database, including 8 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 0.0021 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL11 NM_000641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 9 publications found

Genes affected

IL11 (HGNC:5966): (interleukin 11) The protein encoded by this gene is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor IL6ST (gp130). This cytokine is shown to stimulate the T-cell-dependent development of immunoglobulin-producing B cells. It is also found to support the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00208 (316/152010) while in subpopulation SAS AF = 0.0536 (258/4816). AF 95% confidence interval is 0.0482. There are 8 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	NM_000641.4	MANE Select	c.*1301C>G		3_prime_UTR	Exon 5 of 5	NP_000632.1
	IL11	NM_001267718.2		c.*1301C>G		3_prime_UTR	Exon 4 of 4	NP_001254647.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	ENST00000264563.7	TSL:1 MANE Select	c.*1301C>G		3_prime_UTR	Exon 5 of 5	ENSP00000264563.1

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 151892 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00427

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

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) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.00208 AC: 316 AN: 152010 Hom.: 8 Cov.: 31 AF XY: 0.00304 AC XY: 226 AN XY: 74284

African (AFR) AF: 0.000338 AC: 14 AN: 41430

American (AMR) AF: 0.000524 AC: 8 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00467 AC: 24 AN: 5140

South Asian (SAS) AF: 0.0536 AC: 258 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67998

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00 Hom.: 71370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.64
DANN	Benign	0.41
PhyloP100		-0.71

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: rs1126760; hg19: chr19-55876074;