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GeneBe

2-218660927-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM2_SupportingBP4_Strong

The NM_001079866.2(BCS1L):c.-49-12C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

BCS1L
NM_001079866.2 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001786
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00100

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 33.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCS1LNM_001079866.2 linkuse as main transcriptc.-49-12C>G splice_polypyrimidine_tract_variant, intron_variant ENST00000359273.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCS1LENST00000359273.8 linkuse as main transcriptc.-49-12C>G splice_polypyrimidine_tract_variant, intron_variant 1 NM_001079866.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.0000259
AC:
37
AN:
1427074
Hom.:
0
AF XY:
0.0000281
AC XY:
20
AN XY:
711696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000341
Gnomad4 OTH exome
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxOct 14, 2016The c.-49-12C>G variant in the BCS1L gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant occurs within a region of the promoter and may alter the splice acceptor site in intron 2. However, in silico analysis is inconsistent in its predictions as to whether or not the variant may affect splicing, and in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Additional data from control individuals in the NHLBI Exome Sequencing Project was not available to assess whether c.-49-12C>G may be a common benign variant in the general population. Therefore, we interpret c.-49-12C>G as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
7.5
Dann
Benign
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00018
dbscSNV1_RF
Benign
0.040
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs766996246; hg19: chr2-219525650; API