rs2303561

chr2-218662282-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001079866.2(BCS1L):c.719+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,608,734 control chromosomes in the GnomAD database, including 161,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (24818 hom., cov: 32)
  • Exomes 𝑓: 0.42 (136411 hom.)
• Consequence: BCS1L NM_001079866.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.797

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-218662282-C-T is Benign according to our data. Variant chr2-218662282-C-T is described in ClinVar as [Benign]. Clinvar id is 1291331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCS1L	NM_001079866.2	c.719+22C>T		intron_variant		ENST00000359273.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCS1L	ENST00000359273.8	c.719+22C>T		intron_variant		1	NM_001079866.2	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80953 AN: 151916 Hom.: 24751 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.481

GnomAD3 exomes AF: 0.419 AC: 105259 AN: 251422 Hom.: 24489 AF XY: 0.409 AC XY: 55613 AN XY: 135886

Gnomad AFR exome AF: 0.864

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.427

GnomAD4 exome AF: 0.424 AC: 617165 AN: 1456700 Hom.: 136411 Cov.: 35 AF XY: 0.419 AC XY: 303649 AN XY: 725060

Gnomad4 AFR exome AF: 0.873

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.533 AC: 81080 AN: 152034 Hom.: 24818 Cov.: 32 AF XY: 0.525 AC XY: 39031 AN XY: 74306

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.481

Alfa AF: 0.471 Hom.: 4844

Bravo AF: 0.551

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.2
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs2303561; hg19: chr2-219527005; COSMIC: COSV55306474; COSMIC: COSV55306474;