Genetic Variant ENST00000355432.8:c.1033G>C (chrX-1309488-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000355432.8(CSF2RA):c.1033G>C(p.Gly345Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/16 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. 1 hem. )

Consequence

CSF2RA
ENST00000355432.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

0 publications found

Variant links:

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

CSF2RA Gene-Disease associations (from GenCC):

surfactant metabolism dysfunction, pulmonary, 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
hereditary pulmonary alveolar proteinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CSF2RA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095437795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355432.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF2RA	NM_172245.4	MANE Select	c.*9G>C		3_prime_UTR	Exon 13 of 13	NP_758448.1	P15509-1
CSF2RA	NM_172246.4		c.1033G>C	p.Gly345Arg	missense	Exon 11 of 11	NP_758449.1	P15509-5
CSF2RA	NM_001161530.2		c.*9G>C		3_prime_UTR	Exon 14 of 14	NP_001155002.1	P15509-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF2RA	ENST00000355432.8	TSL:1	c.1033G>C	p.Gly345Arg	missense	Exon 11 of 11	ENSP00000347606.3	P15509-5
CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.*9G>C		3_prime_UTR	Exon 13 of 13	ENSP00000370940.3	P15509-1
CSF2RA	ENST00000381524.8	TSL:1	c.*9G>C		3_prime_UTR	Exon 13 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111830

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0040

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.34

M_CAP

Benign

0.0011

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.1

PhyloP100

-1.0

PROVEAN

Benign

-0.25

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Vest4

0.13

MVP

0.12

ClinPred

0.16

GERP RS

-0.99

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over