22-50446979-C-CGGGCG

Variant names:

• chr22-50446979-C-CGGGCG
• rs963346132
• NM_002972.4:c.*158_*162dupCGCCC

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.*158_*162dupCGCCC		3_prime_UTR	Exon 41 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.*158_*162dupCGCCC		3_prime_UTR	Exon 41 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.*158_*162dupCGCCC		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.*158_*162dupCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000418590.4	TSL:1	c.*158_*162dupCGCCC		3_prime_UTR	Exon 9 of 9	ENSP00000401538.2	H0Y5W8
	SBF1	ENST00000931646.1		c.*158_*162dupCGCCC		3_prime_UTR	Exon 41 of 41	ENSP00000601705.1

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

African (AFR) AF: 0.0152 AC: 243 AN: 15942

American (AMR) AF: 0.00154 AC: 50 AN: 32542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19064

East Asian (EAS) AF: 0.00226 AC: 72 AN: 31862

South Asian (SAS) AF: 0.00272 AC: 165 AN: 60654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34998

Middle Eastern (MID) AF: 0.000822 AC: 2 AN: 2432

European-Non Finnish (NFE) AF: 0.00106 AC: 369 AN: 346744

Other (OTH) AF: 0.00227 AC: 70 AN: 30818

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

African (AFR) AF: 0.0158 AC: 635 AN: 40140

American (AMR) AF: 0.00279 AC: 41 AN: 14718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00136 AC: 6 AN: 4410

South Asian (SAS) AF: 0.00148 AC: 6 AN: 4042

European-Finnish (FIN) AF: 0.000106 AC: 1 AN: 9424

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00148 AC: 98 AN: 66288

Other (OTH) AF: 0.00683 AC: 14 AN: 2050

Alfa AF: 0.00 Hom.: 0

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs963346132; hg19: chr22-50885408;