Genetic Variant NM_000641.4:c.*264T>G (chr19-55365743-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000641.4(IL11):c.*264T>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 0.125 in 500,052 control chromosomes in the GnomAD database, including 4,328 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 0.13 ( 1345 hom., cov: 30)

Exomes 𝑓: 0.12 ( 2983 hom. )

Consequence

IL11
NM_000641.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

13 publications found

Variant links:

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]

IL11 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL11	NM_000641.4 link	c.*264T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000264563.7	NP_000632.1	P20809-1A8K3F7
IL11	NM_001267718.2 link	c.*264T>G		3_prime_UTR_variant	Exon 4 of 4		NP_001254647.1	P20809-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL11	ENST00000264563.7 link	c.*264T>G	3_prime_UTR_variant	Exon 5 of 5	1	NM_000641.4	ENSP00000264563.1	P20809-1
IL11	ENST00000585513.1 link	c.*264T>G	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000467355.1	P20809-1
IL11	ENST00000590625.5 link	c.*264T>G	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000465705.1	P20809-2

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19463

AN:

151764

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.00581

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.123

AC:

42801

AN:

348170

Hom.:

2983

Cov.:

AF XY:

0.119

AC XY:

21854

AN XY:

184240

show subpopulations

African (AFR)

AF:

0.125

AC:

914

AN:

7326

American (AMR)

AF:

0.0844

AC:

846

AN:

10022

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

1206

AN:

10796

East Asian (EAS)

AF:

0.00307

AC:

AN:

19900

South Asian (SAS)

AF:

0.0733

AC:

2780

AN:

37946

European-Finnish (FIN)

AF:

0.179

AC:

4067

AN:

22742

Middle Eastern (MID)

AF:

0.0793

AC:

128

AN:

1614

European-Non Finnish (NFE)

AF:

0.140

AC:

30340

AN:

217426

Other (OTH)

AF:

0.121

AC:

2459

AN:

20398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1709

3418

5126

6835

8544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.128

AC:

19481

AN:

151882

Hom.:

1345

Cov.:

AF XY:

0.128

AC XY:

9503

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.127

AC:

5254

AN:

41390

American (AMR)

AF:

0.0849

AC:

1297

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

391

AN:

3466

East Asian (EAS)

AF:

0.00622

AC:

AN:

5148

South Asian (SAS)

AF:

0.0729

AC:

351

AN:

4816

European-Finnish (FIN)

AF:

0.193

AC:

2039

AN:

10556

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9704

AN:

67928

Other (OTH)

AF:

0.124

AC:

261

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

840

1680

2521

3361

4201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

1356

Bravo

AF:

0.123

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over