rs79251068

Positions:

• chr11-9795868-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030962.4(SBF2):​c.4533A>G​(p.Thr1511=) 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:5
• Conservation: PhyloP100: 1.74

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

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 306582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-9795868-T-C is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBF2	NM_030962.4	c.4533A>G	p.Thr1511=	synonymous_variant	33/40	ENST00000256190.13
SBF2-AS1	NR_036485.1	n.212-11980T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13	c.4533A>G	p.Thr1511=	synonymous_variant	33/40	1	NM_030962.4	P3
SBF2-AS1	ENST00000663578.1	n.237-11980T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.00260 AC: 654 AN: 251216 Hom.: 11 AF XY: 0.00175 AC XY: 238 AN XY: 135802

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00214

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

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00408 Hom.: 2

Bravo AF: 0.0110

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Charcot-Marie-Tooth disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

-

- -

Charcot-Marie-Tooth disease type 4B2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 08, 2018

- -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs79251068; hg19: chr11-9817415;