11-9779054-G-A

Position:

• chr11-9779054-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030962.4(SBF2):​c.*1364C>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 0.63 in 152,478 control chromosomes in the GnomAD database, including 30,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30404 hom., cov: 33)
  • Exomes 𝑓: 0.76 (128 hom.)
• Consequence: SBF2 NM_030962.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-9779054-G-A is Benign according to our data. Variant chr11-9779054-G-A is described in ClinVar as [Benign]. Clinvar id is 306557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBF2	NM_030962.4	c.*1364C>T		3_prime_UTR_variant	40/40	ENST00000256190.13	NP_112224.1
SBF2-AS1	NR_036485.1	n.211+20551G>A		intron_variant, non_coding_transcript_variant
SBF2	NM_001386339.1	c.*1364C>T		3_prime_UTR_variant	41/41		NP_001373268.1
SBF2	NM_001386342.1	c.*1364C>T		3_prime_UTR_variant	39/39		NP_001373271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBF2	ENST00000256190.13	c.*1364C>T		3_prime_UTR_variant	40/40	1	NM_030962.4	ENSP00000256190	P3
SBF2-AS1	ENST00000663578.1	n.236+20551G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95735 AN: 151928 Hom.: 30399 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.762 AC: 329 AN: 432 Hom.: 128 Cov.: 0 AF XY: 0.781 AC XY: 203 AN XY: 260

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.630 AC: 95777 AN: 152046 Hom.: 30404 Cov.: 33 AF XY: 0.632 AC XY: 46991 AN XY: 74346

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.653

Alfa AF: 0.643 Hom.: 38738

Bravo AF: 0.624

Asia WGS AF: 0.598 AC: 2073 AN: 3468

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

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.47

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: rs10118; hg19: chr11-9800601;