22-36922079-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000395.3(CSF2RB):c.-129T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 805,266 control chromosomes in the GnomAD database, including 317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (50 hom., cov: 33)
  • Exomes 𝑓: 0.025 (267 hom.)
• Consequence: CSF2RB NM_000395.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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]

LOC105373023 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-36922079-T-G is Benign according to our data. Variant chr22-36922079-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0196 (2988/152250) while in subpopulation SAS AF= 0.0269 (130/4832). AF 95% confidence interval is 0.0249. There are 50 homozygotes in gnomad4. There are 1493 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.-129T>G		5_prime_UTR_variant	2/14	ENST00000403662.8
LOC105373023	XR_938230.2	n.195-3140A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-129T>G		5_prime_UTR_variant	2/14	5	NM_000395.3	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2991 AN: 152132 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0247 AC: 16141 AN: 653016 Hom.: 267 Cov.: 9 AF XY: 0.0250 AC XY: 8516 AN XY: 340006

Gnomad4 AFR exome AF: 0.00577

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.0613

Gnomad4 EAS exome AF: 0.0000626

Gnomad4 SAS exome AF: 0.0269

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0253

GnomAD4 genome AF: 0.0196 AC: 2988 AN: 152250 Hom.: 50 Cov.: 33 AF XY: 0.0201 AC XY: 1493 AN XY: 74450

Gnomad4 AFR AF: 0.00457

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0194 Hom.: 6

Bravo AF: 0.0178

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.38
Dann	Benign	0.43

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: rs117689490; hg19: chr22-37318121;