2-218660859-A-G

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.-49-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,023,336 control chromosomes in the GnomAD database, including 509,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74618 hom., cov: 32)
  • Exomes 𝑓: 1.0 (434424 hom.)
• Consequence: BCS1L NM_001079866.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389

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=-0.9).
• BP6: Variant 2-218660859-A-G is Benign according to our data. Variant chr2-218660859-A-G is described in ClinVar as [Benign]. Clinvar id is 1179749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCS1L	NM_001079866.2	c.-49-80A>G		intron_variant		ENST00000359273.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCS1L	ENST00000359273.8	c.-49-80A>G		intron_variant		1	NM_001079866.2	P1

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150655 AN: 152220 Hom.: 74575 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

GnomAD4 exome AF: 0.999 AC: 869898 AN: 870998 Hom.: 434424 Cov.: 11 AF XY: 0.999 AC XY: 449136 AN XY: 449616

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.998

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.997

GnomAD4 genome AF: 0.990 AC: 150757 AN: 152338 Hom.: 74618 Cov.: 32 AF XY: 0.990 AC XY: 73760 AN XY: 74498

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.995

Alfa AF: 0.993 Hom.: 10022

Bravo AF: 0.989

Asia WGS AF: 0.996 AC: 3462 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	-0.90
CADD	Benign	1.4
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6722185; hg19: chr2-219525582;