22-50446979-C-CGGGCG

Position:

• chr22-50446979-C-CGGGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002972.4(SBF1):​c.*158_*162dupCGCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 720,700 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (5 hom.)
• Consequence: SBF1 NM_002972.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 -10 ACMG points.

• BP6: Variant 22-50446979-C-CGGGCG is Benign according to our data. Variant chr22-50446979-C-CGGGCG is described in ClinVar as [Likely_benign]. Clinvar id is 1218491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00551 (802/145644) while in subpopulation AFR AF= 0.0158 (635/40140). AF 95% confidence interval is 0.0148. There are 6 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF1	NM_002972.4	c.*158_*162dupCGCCC		3_prime_UTR_variant	41/41	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.*158_*162dupCGCCC		3_prime_UTR_variant	41/41		NP_001397723.1
SBF1	NM_001365819.1	c.*158_*162dupCGCCC		3_prime_UTR_variant	40/40		NP_001352748.1
SBF1	NM_001410795.1	c.*158_*162dupCGCCC		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.*158_*162dupCGCCC		3_prime_UTR_variant	41/41	1	NM_002972.4	ENSP00000370196.2

Frequencies

GnomAD3 genomes AF: 0.00549 AC: 799 AN: 145542 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00279

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00690

GnomAD4 exome AF: 0.00169 AC: 971 AN: 575056 Hom.: 5 Cov.: 7 AF XY: 0.00177 AC XY: 542 AN XY: 306022

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00226

Gnomad4 SAS exome AF: 0.00272

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00551 AC: 802 AN: 145644 Hom.: 6 Cov.: 33 AF XY: 0.00577 AC XY: 410 AN XY: 71090

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.00279

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00148

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.00683

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

Sep 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs963346132; hg19: chr22-50885408;