chr22-36923039-T-G

Variant names:

• chr22-36923039-T-G
• rs2072707
• NM_000395.3:c.77-205T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000395.3(CSF2RB):​c.77-205T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,032 control chromosomes in the GnomAD database, including 34,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34550 hom., cov: 31)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 22-36923039-T-G is Benign according to our data. Variant chr22-36923039-T-G is described in ClinVar as Benign. ClinVar VariationId is 1264734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.77-205T>G		intron_variant	Intron 2 of 13	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.77-205T>G		intron_variant	Intron 2 of 13	5	NM_000395.3	ENSP00000384053.3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101936 AN: 151914 Hom.: 34518 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.671 AC: 102029 AN: 152032 Hom.: 34550 Cov.: 31 AF XY: 0.677 AC XY: 50303 AN XY: 74300

African (AFR) AF: 0.645 AC: 26746 AN: 41462

American (AMR) AF: 0.739 AC: 11291 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4649 AN: 5158

South Asian (SAS) AF: 0.636 AC: 3064 AN: 4820

European-Finnish (FIN) AF: 0.691 AC: 7299 AN: 10570

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44476 AN: 67948

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.661 Hom.: 43629

Bravo AF: 0.675

Asia WGS AF: 0.773 AC: 2688 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 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	-0.99
CADD	Benign	0.40
DANN	Benign	0.42
PhyloP100		-2.1
PromoterAI		-0.0099	Neutral
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: rs2072707; hg19: chr22-37319081;