Variant rs333970 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000369801.1(CSF1):c.1090+5C>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,612,420 control chromosomes in the GnomAD database, including 279,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 20144 hom., cov: 33)

Exomes 𝑓: 0.59 ( 259512 hom. )

Consequence

CSF1
ENST00000369801.1 splice_donor_5th_base, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.402

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]

CSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1095C>A	p.Thr365=	synonymous_variant	6/9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.1095C>A	p.Thr365=	synonymous_variant	6/9	1	NM_000757.6	ENSP00000327513	P4	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1095C>A	p.Thr365=	synonymous_variant	6/9	1		ENSP00000358817	P4	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1090+5C>A		splice_donor_5th_base_variant, intron_variant		1		ENSP00000358816		P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.545-344C>A		intron_variant		5		ENSP00000407317	A1	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73135

AN:

151960

Hom.:

20143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.558

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.515

GnomAD3 exomes

AF:

0.567

AC:

141740

AN:

250112

Hom.:

41927

AF XY:

0.574

AC XY:

77594

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.608

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.431

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.591

AC:

862869

AN:

1460344

Hom.:

259512

Cov.:

AF XY:

0.592

AC XY:

430328

AN XY:

726316

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.600

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.481

AC:

73143

AN:

152076

Hom.:

20144

Cov.:

AF XY:

0.483

AC XY:

35898

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.552

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.651

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.582

Hom.:

44876

Bravo

AF:

0.461

Asia WGS

AF:

0.485

AC:

1690

AN:

3478

EpiCase

AF:

0.612

EpiControl

AF:

0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over