chr11-9779904-G-A

Variant names:

• chr11-9779904-G-A
• rs3829252
• NM_030962.4:c.*514C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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 rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.*514C>T		3_prime_UTR_variant	Exon 40 of 40	ENST00000256190.13	NP_112224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.*514C>T		3_prime_UTR_variant	Exon 40 of 40	1	NM_030962.4	ENSP00000256190.8

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

African (AFR) AF: 0.180 AC: 420 AN: 2328

American (AMR) AF: 0.297 AC: 1155 AN: 3886

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 392 AN: 1106

East Asian (EAS) AF: 0.329 AC: 1377 AN: 4184

South Asian (SAS) AF: 0.201 AC: 1194 AN: 5954

European-Finnish (FIN) AF: 0.432 AC: 825 AN: 1910

Middle Eastern (MID) AF: 0.309 AC: 50 AN: 162

European-Non Finnish (NFE) AF: 0.374 AC: 11125 AN: 29772

Other (OTH) AF: 0.355 AC: 878 AN: 2474

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

African (AFR) AF: 0.217 AC: 9019 AN: 41468

American (AMR) AF: 0.320 AC: 4889 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1657 AN: 5168

South Asian (SAS) AF: 0.202 AC: 975 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5019 AN: 10536

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26872 AN: 67978

Other (OTH) AF: 0.328 AC: 693 AN: 2114

Alfa AF: 0.366 Hom.: 13182

Bravo AF: 0.318

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3829252; hg19: chr11-9801451;