chr1-109917151-C-G

Variant names:

• chr1-109917151-C-G
• rs333967
• NM_000757.6:c.226-142C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000757.6(CSF1):​c.226-142C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 624,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.226-142C>G		intron_variant	Intron 3 of 8	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.226-142C>G		intron_variant	Intron 3 of 8	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000160 AC: 1 AN: 624856 Hom.: 0 AF XY: 0.00000306 AC XY: 1 AN XY: 326570

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16208

American (AMR) AF: 0.00 AC: 0 AN: 24318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35044

South Asian (SAS) AF: 0.00 AC: 0 AN: 53088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2392

European-Non Finnish (NFE) AF: 0.00000245 AC: 1 AN: 407514

Other (OTH) AF: 0.00 AC: 0 AN: 31906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.60
PhyloP100		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs333967; hg19: chr1-110459773;