22-50447066-A-G

Position:

• chr22-50447066-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_002972.4(SBF1):​c.*76T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,340,046 control chromosomes in the GnomAD database, including 609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (39 hom., cov: 33)
  • Exomes 𝑓: 0.027 (570 hom.)
• Consequence: SBF1 NM_002972.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.570

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

SBF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 22-50447066-A-G is Benign according to our data. Variant chr22-50447066-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2524/152170) while in subpopulation NFE AF= 0.0294 (1996/67962). AF 95% confidence interval is 0.0283. There are 39 homozygotes in gnomad4. There are 1126 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF1	NM_002972.4	c.*76T>C		3_prime_UTR_variant	41/41	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.*76T>C		3_prime_UTR_variant	41/41		NP_001397723.1
SBF1	NM_001365819.1	c.*76T>C		3_prime_UTR_variant	40/40		NP_001352748.1
SBF1	NM_001410795.1	c.*76T>C		3_prime_UTR_variant	40/40		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817	c.*76T>C		3_prime_UTR_variant	41/41	1	NM_002972.4	ENSP00000370196.2

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2525 AN: 152052 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.00486

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00981

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0268 AC: 31830 AN: 1187876 Hom.: 570 Cov.: 16 AF XY: 0.0261 AC XY: 15475 AN XY: 592544

Gnomad4 AFR exome AF: 0.00478

Gnomad4 AMR exome AF: 0.00462

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00262

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0166 AC: 2524 AN: 152170 Hom.: 39 Cov.: 33 AF XY: 0.0151 AC XY: 1126 AN XY: 74426

Gnomad4 AFR AF: 0.00484

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00981

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0294

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0208 Hom.: 6

Bravo AF: 0.0161

Asia WGS AF: 0.00202 AC: 7 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

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.90

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: rs1053764; hg19: chr22-50885495;