rs40401

Positions:

• chr5-132060785-C-A
• chr5-132060785-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000588.4(IL3):​c.79C>A​(p.Pro27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P27S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.63

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]

LOC105379174 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15314686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL3	NM_000588.4	c.79C>A	p.Pro27Thr	missense_variant	1/5	ENST00000296870.3	NP_000579.2
LOC105379174	XR_001742531.2	n.211+686G>T		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948784.3	n.398+686G>T		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948785.3	n.228+686G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL3	ENST00000296870.3	c.79C>A	p.Pro27Thr	missense_variant	1/5	1	NM_000588.4	ENSP00000296870	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0080
DANN	Benign	0.90
DEOGEN2	Benign	0.41	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.043
Sift	Benign	0.041	D
Sift4G	Benign	0.10	T
Polyphen		0.78	P
Vest4		0.057
MutPred		0.27		Loss of glycosylation at P27 (P = 0.0211);
MVP		0.28
MPC		0.25
ClinPred		0.31	T
GERP RS		1.2
Varity_R		0.042
gMVP		0.61

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: rs40401; hg19: chr5-131396478; COSMIC: COSV57308641;