rs6000488

Variant names:

• chr22-36925818-G-A
• rs6000488
• NM_000395.3:c.201-169G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-36925818-G-A
• chr22-36925818-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.201-169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,124 control chromosomes in the GnomAD database, including 1,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.12 (1221 hom., cov: 32)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.418
• Publications: 6 publications found

Genes affected

CSF2RB (HGNC:2436): (colony stimulating factor 2 receptor subunit beta) The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]

CSF2RB Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 5

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-36925818-G-A is Benign according to our data. Variant chr22-36925818-G-A is described in ClinVar as Benign. ClinVar VariationId is 1288350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.201-169G>A		intron_variant	Intron 3 of 13	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.201-169G>A		intron_variant	Intron 3 of 13	5	NM_000395.3	ENSP00000384053.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17605 AN: 152006 Hom.: 1221 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17621 AN: 152124 Hom.: 1221 Cov.: 32 AF XY: 0.112 AC XY: 8346 AN XY: 74370

African (AFR) AF: 0.177 AC: 7319 AN: 41450

American (AMR) AF: 0.0819 AC: 1253 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.121 AC: 585 AN: 4826

European-Finnish (FIN) AF: 0.0467 AC: 495 AN: 10592

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 7030 AN: 68008

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.105 Hom.: 1401

Bravo AF: 0.119

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6000488; hg19: chr22-37321860;