11-9779274-T-C

Variant names:

• chr11-9779274-T-C
• rs3751001
• NM_030962.4:c.*1144A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_030962.4(SBF2):​c.*1144A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,750 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (501 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: SBF2 NM_030962.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.50
• Publications: 3 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 11-9779274-T-C is Benign according to our data. Variant chr11-9779274-T-C is described in ClinVar as [Benign]. Clinvar id is 306559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBF2	NM_030962.4	c.*1144A>G		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.*1144A>G		3_prime_UTR_variant	Exon 40 of 40	1	NM_030962.4	ENSP00000256190.8

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6990 AN: 152200 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.0209 AC: 9 AN: 430 Hom.: 0 Cov.: 0 AF XY: 0.0308 AC XY: 8 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: 0.0212 AC: 9 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0459 AC: 6997 AN: 152320 Hom.: 501 Cov.: 32 AF XY: 0.0470 AC XY: 3504 AN XY: 74488

African (AFR) AF: 0.0862 AC: 3583 AN: 41562

American (AMR) AF: 0.0725 AC: 1109 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1637 AN: 5186

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4828

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00532 AC: 362 AN: 68028

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0246 Hom.: 90

Bravo AF: 0.0545

Asia WGS AF: 0.135 AC: 468 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	-0.25
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		2.5
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: rs3751001; hg19: chr11-9800821; COSMIC: COSV56315376; COSMIC: COSV56315376;