11-9779904-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_030962.4(SBF2):c.*514C>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 0.335 in 203,806 control chromosomes in the GnomAD database, including 12,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9200 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3276 hom.)
• Consequence: SBF2 NM_030962.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-9779904-G-A is Benign according to our data. Variant chr11-9779904-G-A is described in ClinVar as [Benign]. Clinvar id is 306564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBF2	NM_030962.4	c.*514C>T		3_prime_UTR_variant	40/40	ENST00000256190.13
SBF2-AS1	NR_036485.1	n.211+21401G>A		intron_variant, non_coding_transcript_variant
SBF2	NM_001386339.1	c.*514C>T		3_prime_UTR_variant	41/41
SBF2	NM_001386342.1	c.*514C>T		3_prime_UTR_variant	39/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13	c.*514C>T		3_prime_UTR_variant	40/40	1	NM_030962.4	P3
SBF2-AS1	ENST00000663578.1	n.236+21401G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50894 AN: 151912 Hom.: 9204 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.336 AC: 17416 AN: 51776 Hom.: 3276 Cov.: 0 AF XY: 0.326 AC XY: 8814 AN XY: 27008

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.335 AC: 50889 AN: 152030 Hom.: 9200 Cov.: 32 AF XY: 0.334 AC XY: 24841 AN XY: 74276

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.328

Alfa AF: 0.372 Hom.: 10228

Bravo AF: 0.318

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	15
Dann	Benign	0.74

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: rs3829252; hg19: chr11-9801451;