chr2-218660409-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001079866.2(BCS1L):​c.-49-530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 153,448 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 0 hom. )

Consequence

BCS1L
NM_001079866.2 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.321
Variant links:
Genes affected
BCS1L (HGNC:1020): (BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone) This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 2-218660409-C-T is Benign according to our data. Variant chr2-218660409-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 559366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00498 (754/151442) while in subpopulation AFR AF= 0.0175 (721/41226). AF 95% confidence interval is 0.0164. There are 11 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCS1LNM_001079866.2 linkuse as main transcriptc.-49-530C>T intron_variant ENST00000359273.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCS1LENST00000359273.8 linkuse as main transcriptc.-49-530C>T intron_variant 1 NM_001079866.2 P1

Frequencies

GnomAD3 genomes
AF:
0.00498
AC:
753
AN:
151324
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0175
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00158
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000590
Gnomad OTH
AF:
0.00192
GnomAD4 exome
AF:
0.00150
AC:
3
AN:
2006
Hom.:
0
Cov.:
0
AF XY:
0.00287
AC XY:
3
AN XY:
1044
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00412
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:
0.00
Gnomad4 OTH exome
AF:
0.0135
GnomAD4 genome
AF:
0.00498
AC:
754
AN:
151442
Hom.:
11
Cov.:
32
AF XY:
0.00477
AC XY:
353
AN XY:
74024
show subpopulations
Gnomad4 AFR
AF:
0.0175
Gnomad4 AMR
AF:
0.00158
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000590
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00423
Hom.:
0
Bravo
AF:
0.00574
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicFeb 29, 2016- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
5.1
DANN
Benign
0.60

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.

Other links and lift over

dbSNP: rs115162602; hg19: chr2-219525132; API