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2-218660148-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BP4

The ENST00000392109.5(BCS1L):c.-120A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152236 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Consequence

BCS1L
ENST00000392109.5 5_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:2

Conservation

PhyloP100: -0.878

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance.

PP5
?
Variant 2-218660148-A-G is Pathogenic according to our data. Variant chr2-218660148-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 553134.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Likely_pathogenic=1, Pathogenic=1}.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCS1LNM_001079866.2 linkuse as main transcriptc.-50+405A>G intron_variant ENST00000359273.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCS1LENST00000359273.8 linkuse as main transcriptc.-50+405A>G intron_variant 1 NM_001079866.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000147
Gnomad OTH
AF:
0.00
Bravo
AF:
0.0000302

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:2Uncertain:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

GRACILE syndrome Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Uncertain significance, criteria provided, single submitterclinical testingCounsylJul 28, 2017- -
Mitochondrial complex III deficiency nuclear type 1 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingBaylor GeneticsApr 10, 2018This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJun 07, 2022This variant occurs in a non-coding region of the BCS1L gene. It does not change the encoded amino acid sequence of the BCS1L protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with mitochondrial complex III deficiency (PMID: 19389488, 28128857, 28496993). ClinVar contains an entry for this variant (Variation ID: 553134). Studies have shown that this variant alters BCS1L gene expression (PMID: 19389488). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
9.9
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.69
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.69
Position offset: -1

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: rs898301590; hg19: chr2-219524871; API