chr22-50447030-G-T

Variant names:

• chr22-50447030-G-T
• rs148435544
• NM_002972.4:c.*112C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002972.4(SBF1):​c.*112C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SBF1 NM_002972.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002972.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF1	NM_002972.4	MANE Select	c.*112C>A		3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.*112C>A		3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.*112C>A		3_prime_UTR	Exon 40 of 40	NP_001352748.1	O95248-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF1	ENST00000380817.8	TSL:1 MANE Select	c.*112C>A		3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.*112C>A		3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.*112C>A		3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 786000 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 403176

African (AFR) AF: 0.00 AC: 0 AN: 19762

American (AMR) AF: 0.00 AC: 0 AN: 31868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18966

East Asian (EAS) AF: 0.00 AC: 0 AN: 32730

South Asian (SAS) AF: 0.00 AC: 0 AN: 62296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2772

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 536330

Other (OTH) AF: 0.00 AC: 0 AN: 37460

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.8
DANN	Benign	0.94
PhyloP100		-0.38

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: rs148435544; hg19: chr22-50885459;