5-132060993-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000588.4(IL3):​c.189C>T​(p.Asp63Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,178 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 13 hom. )

Consequence

IL3
NM_000588.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
IL3 (HGNC:6011): (interleukin 3) The protein encoded by this gene is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 5-132060993-C-T is Benign according to our data. Variant chr5-132060993-C-T is described in ClinVar as [Benign]. Clinvar id is 715603.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.08 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00625 (952/152346) while in subpopulation AFR AF= 0.0213 (885/41586). AF 95% confidence interval is 0.0201. There are 8 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 952 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL3NM_000588.4 linkc.189C>T p.Asp63Asp synonymous_variant Exon 2 of 5 ENST00000296870.3 NP_000579.2 P08700
LOC105379174XR_001742531.2 linkn.211+478G>A intron_variant Intron 2 of 4
LOC105379174XR_948784.3 linkn.398+478G>A intron_variant Intron 2 of 2
LOC105379174XR_948785.3 linkn.228+478G>A intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL3ENST00000296870.3 linkc.189C>T p.Asp63Asp synonymous_variant Exon 2 of 5 1 NM_000588.4 ENSP00000296870.2 P08700

Frequencies

GnomAD3 genomes
AF:
0.00627
AC:
955
AN:
152228
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0214
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00281
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00169
AC:
424
AN:
251342
Hom.:
5
AF XY:
0.00135
AC XY:
183
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.0225
Gnomad AMR exome
AF:
0.000954
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.000669
AC:
978
AN:
1461832
Hom.:
13
Cov.:
31
AF XY:
0.000571
AC XY:
415
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0226
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000710
Gnomad4 OTH exome
AF:
0.00131
GnomAD4 genome
AF:
0.00625
AC:
952
AN:
152346
Hom.:
8
Cov.:
33
AF XY:
0.00616
AC XY:
459
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0213
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00177
Hom.:
0
Bravo
AF:
0.00720
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 06, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.17
DANN
Benign
0.21

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs55698209; hg19: chr5-131396686; API