NM_030962.4:c.*1515G>A

Variant names:

• chr11-9778903-C-T
• rs1045634
• NM_030962.4:c.*1515G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030962.4(SBF2):​c.*1515G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,540 control chromosomes in the GnomAD database, including 9,206 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 (9160 hom., cov: 33)
  • Exomes 𝑓: 0.48 (46 hom.)
• Consequence: SBF2 NM_030962.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• 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.*1515G>A		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.*1515G>A		3_prime_UTR_variant	Exon 40 of 40	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50785 AN: 151986 Hom.: 9164 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.479 AC: 208 AN: 434 Hom.: 46 Cov.: 0 AF XY: 0.465 AC XY: 121 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.481 AC: 205 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.334 AC: 50780 AN: 152106 Hom.: 9160 Cov.: 33 AF XY: 0.334 AC XY: 24805 AN XY: 74360

African (AFR) AF: 0.215 AC: 8926 AN: 41502

American (AMR) AF: 0.319 AC: 4872 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1281 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1655 AN: 5186

South Asian (SAS) AF: 0.202 AC: 973 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5043 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26867 AN: 67978

Other (OTH) AF: 0.329 AC: 692 AN: 2106

Alfa AF: 0.369 Hom.: 18578

Bravo AF: 0.317

Asia WGS AF: 0.235 AC: 819 AN: 3474

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	-0.61
CADD	Benign	14
DANN	Benign	0.77
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: rs1045634; hg19: chr11-9800450;