NM_002972.4:c.5637C>G

Variant names:

• chr22-50447187-G-C
• NM_002972.4:c.5637C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_002972.4(SBF1):​c.5637C>G​(p.Ala1879Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SBF1 NM_002972.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-50447187-G-C is Benign according to our data. Variant chr22-50447187-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2028977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.441 with no splicing effect.

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.5637C>G	p.Ala1879Ala	synonymous	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.5640C>G	p.Ala1880Ala	synonymous	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.5562C>G	p.Ala1854Ala	synonymous	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.5637C>G	p.Ala1879Ala	synonymous	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.1233C>G	p.Ala411Ala	synonymous	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.5697C>G	p.Ala1899Ala	synonymous	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr22-50885616;