rs145194651

Variant names:

• chr19-55366073-C-A
• rs145194651
• NM_000641.4:c.534G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55366073-C-A
• chr19-55366073-C-G
• chr19-55366073-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000641.4(IL11):​c.534G>T​(p.Leu178Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,597,640 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0063 (36 hom.)
• Consequence: IL11 NM_000641.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-55366073-C-A is Benign according to our data. Variant chr19-55366073-C-A is described in ClinVar as Benign. ClinVar VariationId is 774358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	NM_000641.4	MANE Select	c.534G>T	p.Leu178Leu	synonymous	Exon 5 of 5	NP_000632.1	A8K3F7
	IL11	NM_001267718.2		c.297G>T	p.Leu99Leu	synonymous	Exon 4 of 4	NP_001254647.1	P20809-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL11	ENST00000264563.7	TSL:1 MANE Select	c.534G>T	p.Leu178Leu	synonymous	Exon 5 of 5	ENSP00000264563.1	P20809-1
	IL11	ENST00000585513.1	TSL:1	c.534G>T	p.Leu178Leu	synonymous	Exon 5 of 5	ENSP00000467355.1	P20809-1
	IL11	ENST00000590625.5	TSL:2	c.297G>T	p.Leu99Leu	synonymous	Exon 4 of 4	ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152102 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00438 AC: 940 AN: 214432 AF XY: 0.00464

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.00802

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.00733

Gnomad OTH exome AF: 0.00340

GnomAD4 exome AF: 0.00632 AC: 9134 AN: 1445420 Hom.: 36 Cov.: 32 AF XY: 0.00624 AC XY: 4479 AN XY: 717618

African (AFR) AF: 0.00108 AC: 36 AN: 33196

American (AMR) AF: 0.00222 AC: 95 AN: 42780

Ashkenazi Jewish (ASJ) AF: 0.00851 AC: 219 AN: 25724

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39042

South Asian (SAS) AF: 0.00133 AC: 111 AN: 83480

European-Finnish (FIN) AF: 0.00225 AC: 114 AN: 50628

Middle Eastern (MID) AF: 0.00247 AC: 13 AN: 5272

European-Non Finnish (NFE) AF: 0.00748 AC: 8267 AN: 1105584

Other (OTH) AF: 0.00464 AC: 277 AN: 59714

GnomAD4 genome AF: 0.00441 AC: 671 AN: 152220 Hom.: 3 Cov.: 31 AF XY: 0.00407 AC XY: 303 AN XY: 74420

African (AFR) AF: 0.00142 AC: 59 AN: 41534

American (AMR) AF: 0.00301 AC: 46 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00724 AC: 492 AN: 67998

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00513 Hom.: 2

Bravo AF: 0.00443

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs145194651; hg19: chr19-55877441;