rs333970

chr1-109923716-C-Achr1-109923716-C-Gchr1-109923716-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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]

ACMG classification

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	UniProt
CSF1	NM_000757.6	c.1095C>A	p.Thr365=	synonymous_variant	6/9	ENST00000329608.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11	c.1095C>A	p.Thr365=	synonymous_variant	6/9	1	NM_000757.6	P4
CSF1	ENST00000369802.7	c.1095C>A	p.Thr365=	synonymous_variant	6/9	1		P4
CSF1	ENST00000369801.1	c.1090+5C>A		splice_donor_5th_base_variant, intron_variant		1
CSF1	ENST00000420111.6	c.545-344C>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73135 AN: 151960 Hom.: 20143 Cov.: 33

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

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.: 73 AF XY: 0.592 AC XY: 430328 AN XY: 726316

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.: 33 AF XY: 0.483 AC XY: 35898 AN XY: 74344

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

Other links and lift over

dbSNP: rs333970; hg19: chr1-110466338; COSMIC: COSV60032931; COSMIC: COSV60032931;