Variant 11-9779103-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_030962.4(SBF2):c.*1315A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 152,342 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0067 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SBF2
NM_030962.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

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 links:

SBF2-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

SBF2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00667 (1016/152342) while in subpopulation AFR AF= 0.0233 (968/41588). AF 95% confidence interval is 0.0221. There are 9 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SBF2	NM_030962.4 linkuse as main transcript	c.*1315A>C	3_prime_UTR_variant	40/40	ENST00000256190.13
SBF2-AS1	NR_036485.1 linkuse as main transcript	n.211+20600T>G	intron_variant, non_coding_transcript_variant
SBF2	NM_001386339.1 linkuse as main transcript	c.*1315A>C	3_prime_UTR_variant	41/41
SBF2	NM_001386342.1 linkuse as main transcript	c.*1315A>C	3_prime_UTR_variant	39/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13 linkuse as main transcript	c.*1315A>C		3_prime_UTR_variant	40/40	1	NM_030962.4	P3	Q86WG5-1
SBF2-AS1	ENST00000663578.1 linkuse as main transcript	n.236+20600T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00667

AC:

1016

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00670

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00667

AC:

1016

AN:

152342

Hom.:

Cov.:

AF XY:

0.00628

AC XY:

468

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.00202

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00317

Hom.:

Bravo

AF:

0.00762

Asia WGS

AF:

0.00145

AC:

AN:

3468

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4B2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over