rs3918001

chr1-36466902-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000373103.5(CSF3R):c.2047G>A(p.Gly683Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00906 in 1,613,922 control chromosomes in the GnomAD database, including 910 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (485 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (425 hom.)
• Consequence: CSF3R ENST00000373103.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.797

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013715625).
• BP6: Variant 1-36466902-C-T is Benign according to our data. Variant chr1-36466902-C-T is described in ClinVar as [Benign]. Clinvar id is 262792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF3R	NM_000760.4	c.2041-75G>A		intron_variant		ENST00000373106.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF3R	ENST00000373106.6	c.2041-75G>A		intron_variant		1	NM_000760.4	P1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6741 AN: 152154 Hom.: 483 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.0335

GnomAD3 exomes AF: 0.0120 AC: 2944 AN: 245468 Hom.: 182 AF XY: 0.00930 AC XY: 1245 AN XY: 133820

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00834

Gnomad ASJ exome AF: 0.00151

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0000931

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.00845

GnomAD4 exome AF: 0.00537 AC: 7856 AN: 1461650 Hom.: 425 Cov.: 31 AF XY: 0.00479 AC XY: 3483 AN XY: 727132

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0444 AC: 6763 AN: 152272 Hom.: 485 Cov.: 33 AF XY: 0.0432 AC XY: 3220 AN XY: 74454

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.00846 Hom.: 180

Bravo AF: 0.0499

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.140 AC: 616

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.0149 AC: 1810

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00267

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

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.85
Dann	Uncertain	0.99
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.035
Sift	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0040	B
Vest4		0.046
MutPred		0.23		Loss of sheet (P = 0.0126);
MPC		0.39
ClinPred		0.0074	T
GERP RS		-2.7
gMVP		0.30

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: rs3918001; hg19: chr1-36932503;