NM_002972.4:c.*112C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002972.4(SBF1):​c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 938,200 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (31 hom.)
• Consequence: SBF1 NM_002972.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 22-50447030-G-A is Benign according to our data. Variant chr22-50447030-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1193044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00596 (908/152254) while in subpopulation NFE AF = 0.00871 (592/67986). AF 95% confidence interval is 0.00813. There are 3 homozygotes in GnomAd4. There are 476 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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>T		3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.*112C>T		3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.*112C>T		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>T		3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.*112C>T		3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.*112C>T		3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

Frequencies

GnomAD3 genomes AF: 0.00596 AC: 907 AN: 152136 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00871

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00681 AC: 5352 AN: 785946 Hom.: 31 Cov.: 11 AF XY: 0.00669 AC XY: 2697 AN XY: 403148

African (AFR) AF: 0.00116 AC: 23 AN: 19762

American (AMR) AF: 0.00226 AC: 72 AN: 31868

Ashkenazi Jewish (ASJ) AF: 0.00285 AC: 54 AN: 18964

East Asian (EAS) AF: 0.0000306 AC: 1 AN: 32730

South Asian (SAS) AF: 0.00120 AC: 75 AN: 62296

European-Finnish (FIN) AF: 0.0127 AC: 557 AN: 43810

Middle Eastern (MID) AF: 0.00144 AC: 4 AN: 2772

European-Non Finnish (NFE) AF: 0.00815 AC: 4371 AN: 536284

Other (OTH) AF: 0.00521 AC: 195 AN: 37460

GnomAD4 genome AF: 0.00596 AC: 908 AN: 152254 Hom.: 3 Cov.: 33 AF XY: 0.00639 AC XY: 476 AN XY: 74446

African (AFR) AF: 0.00159 AC: 66 AN: 41550

American (AMR) AF: 0.00425 AC: 65 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00871 AC: 592 AN: 67986

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.0106 Hom.: 1

Bravo AF: 0.00453

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	-0.68
CADD	Benign	8.6
DANN	Benign	0.96
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

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;