ENST00000355432.8:c.1073G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000355432.8(CSF2RA):c.1073G>T(p.Arg358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,613,540 control chromosomes in the GnomAD database, including 10,306 homozygotes. There are 71,282 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R358Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.14 ( 2542 hom., 10929 hem., cov: 33)

Exomes 𝑓: 0.078 ( 7764 hom. 60353 hem. )

Consequence

CSF2RA
ENST00000355432.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.816

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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000355432.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031292737).

BP6

Variant X-1309528-G-T is Benign according to our data. Variant chrX-1309528-G-T is described in ClinVar as Benign. ClinVar VariationId is 226543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

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.*49G>T		3_prime_UTR	Exon 13 of 13	NP_758448.1	P15509-1
CSF2RA	NM_172246.4		c.1073G>T	p.Arg358Leu	missense	Exon 11 of 11	NP_758449.1	P15509-5
CSF2RA	NM_001161530.2		c.*49G>T		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.1073G>T	p.Arg358Leu	missense	Exon 11 of 11	ENSP00000347606.3	P15509-5
CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.*49G>T		3_prime_UTR	Exon 13 of 13	ENSP00000370940.3	P15509-1
CSF2RA	ENST00000381524.8	TSL:1	c.*49G>T		3_prime_UTR	Exon 13 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21955

AN:

152040

Hom.:

2527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.0787

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.138

GnomAD2 exomes

AF:

0.113

AC:

28443

AN:

251160

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0998

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0711

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0964

GnomAD4 exome

AF:

0.0780

AC:

113991

AN:

1461382

Hom.:

7764

Cov.:

AF XY:

0.0830

AC XY:

60353

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.315

AC:

10531

AN:

33458

American (AMR)

AF:

0.101

AC:

4514

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0444

AC:

1160

AN:

26130

East Asian (EAS)

AF:

0.138

AC:

5485

AN:

39694

South Asian (SAS)

AF:

0.261

AC:

22506

AN:

86228

European-Finnish (FIN)

AF:

0.0679

AC:

3627

AN:

53420

Middle Eastern (MID)

AF:

0.145

AC:

838

AN:

5762

European-Non Finnish (NFE)

AF:

0.0534

AC:

59399

AN:

1111608

Other (OTH)

AF:

0.0982

AC:

5931

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5946

11891

17837

23782

29728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2522

5044

7566

10088

12610

<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:

0.145

AC:

22006

AN:

152158

Hom.:

2542

Cov.:

AF XY:

0.147

AC XY:

10929

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.312

AC:

12956

AN:

41492

American (AMR)

AF:

0.114

AC:

1743

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.138

AC:

716

AN:

5174

South Asian (SAS)

AF:

0.282

AC:

1359

AN:

4822

European-Finnish (FIN)

AF:

0.0787

AC:

834

AN:

10596

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0561

AC:

3814

AN:

67992

Other (OTH)

AF:

0.138

AC:

291

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

865

1730

2595

3460

4325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.149

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CSF2RA-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.99

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.59

(source)

DANN

Benign

0.13

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.97

PhyloP100

-0.82

PROVEAN

Benign

2.1

REVEL

Benign

0.042

Sift

Pathogenic

0.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over