NM_000757.6:c.396+435C>T

Variant names:

• chr1-109917898-C-T
• rs333968
• NM_000757.6:c.396+435C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000757.6(CSF1):​c.396+435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,130 control chromosomes in the GnomAD database, including 47,372 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (47372 hom., cov: 32)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.396+435C>T		intron_variant	Intron 4 of 8	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.396+435C>T		intron_variant	Intron 4 of 8	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116906 AN: 152014 Hom.: 47365 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.800

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 116944 AN: 152130 Hom.: 47372 Cov.: 32 AF XY: 0.768 AC XY: 57111 AN XY: 74352

African (AFR) AF: 0.488 AC: 20235 AN: 41454

American (AMR) AF: 0.788 AC: 12047 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3118 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4079 AN: 5180

South Asian (SAS) AF: 0.804 AC: 3869 AN: 4812

European-Finnish (FIN) AF: 0.881 AC: 9324 AN: 10582

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61561 AN: 68020

Other (OTH) AF: 0.801 AC: 1691 AN: 2112

Alfa AF: 0.860 Hom.: 176513

Bravo AF: 0.751

Asia WGS AF: 0.781 AC: 2717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.70
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs333968; hg19: chr1-110460520;