chr2-218660612-C-T

Position:

• chr2-218660612-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001079866.2(BCS1L):​c.-49-327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 238,626 control chromosomes in the GnomAD database, including 35,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (19742 hom., cov: 32)
  • Exomes 𝑓: 0.58 (15325 hom.)
• Consequence: BCS1L NM_001079866.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.182

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-218660612-C-T is Benign according to our data. Variant chr2-218660612-C-T is described in ClinVar as [Benign]. Clinvar id is 669695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCS1L	NM_001079866.2	c.-49-327C>T		intron_variant		ENST00000359273.8	NP_001073335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCS1L	ENST00000359273.8	c.-49-327C>T		intron_variant		1	NM_001079866.2	ENSP00000352219	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70944 AN: 151906 Hom.: 19743 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.577 AC: 50003 AN: 86602 Hom.: 15325 Cov.: 0 AF XY: 0.587 AC XY: 26077 AN XY: 44388

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.592

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.467 AC: 70935 AN: 152024 Hom.: 19742 Cov.: 32 AF XY: 0.475 AC XY: 35284 AN XY: 74326

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.519

Alfa AF: 0.508 Hom.: 2655

Bravo AF: 0.449

Asia WGS AF: 0.699 AC: 2429 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3770218; hg19: chr2-219525335;