1-109923833-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000757.6(CSF1):​c.1212G>A​(p.Arg404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,613,632 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

CSF1
NM_000757.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340
Variant links:
Genes affected
CSF1 (HGNC:2432): (colony stimulating factor 1) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 1-109923833-G-A is Benign according to our data. Variant chr1-109923833-G-A is described in ClinVar as [Benign]. Clinvar id is 736032.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.034 with no splicing effect.
BS2
High AC in GnomAd4 at 289 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CSF1NM_000757.6 linkuse as main transcriptc.1212G>A p.Arg404= synonymous_variant 6/9 ENST00000329608.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CSF1ENST00000329608.11 linkuse as main transcriptc.1212G>A p.Arg404= synonymous_variant 6/91 NM_000757.6 P4P09603-1
CSF1ENST00000369802.7 linkuse as main transcriptc.1212G>A p.Arg404= synonymous_variant 6/91 P4P09603-1
CSF1ENST00000369801.1 linkuse as main transcriptc.1090+122G>A intron_variant 1 P09603-2
CSF1ENST00000420111.6 linkuse as main transcriptc.545-227G>A intron_variant 5 A1P09603-3

Frequencies

GnomAD3 genomes
AF:
0.00189
AC:
287
AN:
152170
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00659
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
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:
0.0000294
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000455
AC:
114
AN:
250520
Hom.:
1
AF XY:
0.000273
AC XY:
37
AN XY:
135522
show subpopulations
Gnomad AFR exome
AF:
0.00648
Gnomad AMR exome
AF:
0.000232
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000146
AC:
214
AN:
1461346
Hom.:
1
Cov.:
77
AF XY:
0.000110
AC XY:
80
AN XY:
726986
show subpopulations
Gnomad4 AFR exome
AF:
0.00526
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000398
GnomAD4 genome
AF:
0.00190
AC:
289
AN:
152286
Hom.:
1
Cov.:
33
AF XY:
0.00180
AC XY:
134
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00662
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00103
Hom.:
0
Bravo
AF:
0.00190
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.0
DANN
Benign
0.39

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: rs149423163; hg19: chr1-110466455; API