chr5-132060749-C-A

Position:

• chr5-132060749-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000588.4(IL3):​c.43C>A​(p.Arg15Ser) 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. R15H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02983278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL3	NM_000588.4	c.43C>A	p.Arg15Ser	missense_variant	1/5	ENST00000296870.3	NP_000579.2
LOC105379174	XR_001742531.2	n.211+722G>T		intron_variant
LOC105379174	XR_948784.3	n.398+722G>T		intron_variant
LOC105379174	XR_948785.3	n.228+722G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL3	ENST00000296870.3	c.43C>A	p.Arg15Ser	missense_variant	1/5	1	NM_000588.4	ENSP00000296870.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.045
DANN	Benign	0.24
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.0050
Sift	Benign	0.97	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.20		Gain of disorder (P = 0.1019);
MVP		0.13
MPC		0.25
ClinPred		0.030	T
GERP RS		-3.2
Varity_R		0.054
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-131396442;