rs3917979

chr1-36471791-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000760.4(CSF3R):c.1072-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 810,694 control chromosomes in the GnomAD database, including 18,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4245 hom., cov: 32)
  • Exomes 𝑓: 0.20 (14413 hom.)
• Consequence: CSF3R NM_000760.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.822

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-36471791-T-C is Benign according to our data. Variant chr1-36471791-T-C is described in ClinVar as [Benign]. Clinvar id is 1181291.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF3R	NM_000760.4	c.1072-145A>G		intron_variant		ENST00000373106.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF3R	ENST00000373106.6	c.1072-145A>G		intron_variant		1	NM_000760.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34555 AN: 151862 Hom.: 4239 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.202 AC: 133190 AN: 658714 Hom.: 14413 Cov.: 9 AF XY: 0.206 AC XY: 70322 AN XY: 342004

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.228 AC: 34589 AN: 151980 Hom.: 4245 Cov.: 32 AF XY: 0.231 AC XY: 17143 AN XY: 74282

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.234

Alfa AF: 0.198 Hom.: 4004

Bravo AF: 0.224

Asia WGS AF: 0.292 AC: 1012 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.69
Dann	Benign	0.81

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: rs3917979; hg19: chr1-36937392;