1-109917151-C-T

Variant names:

• chr1-109917151-C-T
• rs333967
• NM_000757.6:c.226-142C>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.226-142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 775,494 control chromosomes in the GnomAD database, including 47,357 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 0.28 (7262 hom., cov: 31)
  • Exomes 𝑓: 0.35 (40095 hom.)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42888 AN: 151670 Hom.: 7258 Cov.: 31

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.353 AC: 220114 AN: 623704 Hom.: 40095 AF XY: 0.356 AC XY: 116151 AN XY: 325934

African (AFR) AF: 0.0877 AC: 1421 AN: 16200

American (AMR) AF: 0.421 AC: 10222 AN: 24268

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 6156 AN: 15160

East Asian (EAS) AF: 0.390 AC: 13643 AN: 35010

South Asian (SAS) AF: 0.425 AC: 22545 AN: 53022

European-Finnish (FIN) AF: 0.285 AC: 11147 AN: 39154

Middle Eastern (MID) AF: 0.327 AC: 782 AN: 2392

European-Non Finnish (NFE) AF: 0.352 AC: 143274 AN: 406640

Other (OTH) AF: 0.343 AC: 10924 AN: 31858

GnomAD4 genome AF: 0.283 AC: 42904 AN: 151790 Hom.: 7262 Cov.: 31 AF XY: 0.284 AC XY: 21029 AN XY: 74158

African (AFR) AF: 0.0930 AC: 3850 AN: 41414

American (AMR) AF: 0.359 AC: 5485 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2074 AN: 5102

South Asian (SAS) AF: 0.443 AC: 2131 AN: 4806

European-Finnish (FIN) AF: 0.273 AC: 2874 AN: 10532

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23942 AN: 67888

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.297 Hom.: 950

Bravo AF: 0.282

Asia WGS AF: 0.408 AC: 1417 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	7.7
DANN	Benign	0.61
PhyloP100		0.50
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: rs333967; hg19: chr1-110459773; COSMIC: COSV60035901;