chr22-50463961-A-G

Variant names:

• chr22-50463961-A-G
• rs5771040
• NM_002972.4:c.1749+368T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002972.4(SBF1):​c.1749+368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,106 control chromosomes in the GnomAD database, including 38,165 homozygotes. 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: 𝑓 0.70 (38165 hom., cov: 33)
• Consequence: SBF1 NM_002972.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 5 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF1	NM_002972.4	c.1749+368T>C		intron_variant	Intron 15 of 40	ENST00000380817.8	NP_002963.2
SBF1	NM_001410794.1	c.1752+368T>C		intron_variant	Intron 15 of 40		NP_001397723.1
SBF1	NM_001365819.1	c.1752+368T>C		intron_variant	Intron 15 of 39		NP_001352748.1
SBF1	NM_001410795.1	c.1749+368T>C		intron_variant	Intron 15 of 39		NP_001397724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF1	ENST00000380817.8	c.1749+368T>C		intron_variant	Intron 15 of 40	1	NM_002972.4	ENSP00000370196.2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106600 AN: 151988 Hom.: 38106 Cov.: 33

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.692

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.702 AC: 106724 AN: 152106 Hom.: 38165 Cov.: 33 AF XY: 0.705 AC XY: 52398 AN XY: 74356

African (AFR) AF: 0.795 AC: 32981 AN: 41482

American (AMR) AF: 0.702 AC: 10737 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2160 AN: 3468

East Asian (EAS) AF: 0.962 AC: 4992 AN: 5188

South Asian (SAS) AF: 0.544 AC: 2618 AN: 4816

European-Finnish (FIN) AF: 0.715 AC: 7564 AN: 10586

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43295 AN: 67958

Other (OTH) AF: 0.697 AC: 1474 AN: 2116

Alfa AF: 0.668 Hom.: 95758

Bravo AF: 0.712

Asia WGS AF: 0.791 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs5771040; hg19: chr22-50902390; COSMIC: COSV62366551; COSMIC: COSV62366551;