rs150501885

chr1-36466372-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000760.4(CSF3R):c.2496G>A(p.Ala832=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000758 in 1,612,962 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (8 hom.)
• Consequence: CSF3R NM_000760.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.570

Genes affected

CSF3R (HGNC:2439): (colony stimulating factor 3 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-36466372-C-T is Benign according to our data. Variant chr1-36466372-C-T is described in ClinVar as [Benign]. Clinvar id is 434832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000722 (110/152300) while in subpopulation EAS AF= 0.0145 (75/5174). AF 95% confidence interval is 0.0119. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF3R	NM_000760.4	c.2496G>A	p.Ala832=	synonymous_variant	17/17	ENST00000373106.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF3R	ENST00000373106.6	c.2496G>A	p.Ala832=	synonymous_variant	17/17	1	NM_000760.4	P1

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 110 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00155 AC: 387 AN: 250282 Hom.: 5 AF XY: 0.00152 AC XY: 206 AN XY: 135420

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0166

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000761 AC: 1112 AN: 1460662 Hom.: 8 Cov.: 31 AF XY: 0.000761 AC XY: 553 AN XY: 726654

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0117

Gnomad4 SAS exome AF: 0.000975

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000457

Gnomad4 OTH exome AF: 0.000830

GnomAD4 genome AF: 0.000722 AC: 110 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000765 AC XY: 57 AN XY: 74482

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00105

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 24, 2019

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.5
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs150501885; hg19: chr1-36931973; COSMIC: COSV105898408; COSMIC: COSV105898408;