rs79251068

Variant names:

• chr11-9795868-T-C
• rs79251068
• NM_030962.4:c.4533A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030962.4(SBF2):​c.4533A>G​(p.Thr1511Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,820 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (24 hom.)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 11-9795868-T-C is Benign according to our data. Variant chr11-9795868-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 306582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00975 (1484/152270) while in subpopulation AFR AF = 0.034 (1412/41544). AF 95% confidence interval is 0.0325. There are 20 homozygotes in GnomAd4. There are 709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. 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
	SBF2	NM_030962.4	MANE Select	c.4533A>G	p.Thr1511Thr	synonymous	Exon 33 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.4629A>G	p.Thr1543Thr	synonymous	Exon 34 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.4569A>G	p.Thr1523Thr	synonymous	Exon 34 of 41	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.4533A>G	p.Thr1511Thr	synonymous	Exon 33 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000689128.1		c.4629A>G	p.Thr1543Thr	synonymous	Exon 34 of 41	ENSP00000509587.1	A0A8I5KQ02
	SBF2	ENST00000675281.2		c.4608A>G	p.Thr1536Thr	synonymous	Exon 34 of 41	ENSP00000502491.1	A0A6Q8PH13

Frequencies

GnomAD3 genomes AF: 0.00976 AC: 1485 AN: 152152 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00260 AC: 654 AN: 251216 AF XY: 0.00175

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.000888 AC: 1298 AN: 1461550 Hom.: 24 Cov.: 31 AF XY: 0.000809 AC XY: 588 AN XY: 727084

African (AFR) AF: 0.0319 AC: 1067 AN: 33462

American (AMR) AF: 0.00154 AC: 69 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111882

Other (OTH) AF: 0.00214 AC: 129 AN: 60392

GnomAD4 genome AF: 0.00975 AC: 1484 AN: 152270 Hom.: 20 Cov.: 32 AF XY: 0.00952 AC XY: 709 AN XY: 74456

African (AFR) AF: 0.0340 AC: 1412 AN: 41544

American (AMR) AF: 0.00347 AC: 53 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00417 Hom.: 4

Bravo AF: 0.0110

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Charcot-Marie-Tooth disease type 4B2 (2)
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		1.7
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: rs79251068; hg19: chr11-9817415;