22-36922133-C-T

Position:

• chr22-36922133-C-T

Variant summary

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

The NM_000395.3(CSF2RB):​c.-75C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,371,378 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (129 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1396 hom.)
• Consequence: CSF2RB NM_000395.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-36922133-C-T is Benign according to our data. Variant chr22-36922133-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.-75C>T		5_prime_UTR_variant	2/14	ENST00000403662.8
LOC105373023	XR_938230.2	n.195-3194G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-75C>T		5_prime_UTR_variant	2/14	5	NM_000395.3	P1
CSF2RB	ENST00000406230.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5566 AN: 152182 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0450 AC: 54851 AN: 1219078 Hom.: 1396 Cov.: 17 AF XY: 0.0455 AC XY: 27686 AN XY: 608144

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0247

Gnomad4 EAS exome AF: 0.0374

Gnomad4 SAS exome AF: 0.0520

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0467

Gnomad4 OTH exome AF: 0.0440

GnomAD4 genome AF: 0.0366 AC: 5569 AN: 152300 Hom.: 129 Cov.: 33 AF XY: 0.0370 AC XY: 2752 AN XY: 74458

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0384

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0347 Hom.: 17

Bravo AF: 0.0337

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs117937233; hg19: chr22-37318175;