rs6722185

Variant names:

• chr2-218660859-A-G
• rs6722185
• NM_001079866.2:c.-49-80A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-218660859-A-G
• chr2-218660859-A-C
• chr2-218660859-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374085.1(BCS1L):​c.-129A>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 0.997 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_001374085.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.389
• Publications: 4 publications found

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]

BCS1L Gene-Disease associations (from GenCC):

• Bjornstad syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen, Ambry Genetics
• GRACILE syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial complex III deficiency nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal tubulopathy-encephalopathy-liver failure syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1179749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374085.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCS1L	NM_001079866.2	MANE Select	c.-49-80A>G		intron	N/A	NP_001073335.1	Q9Y276
	BCS1L	NM_001374085.1		c.-129A>G		5_prime_UTR	Exon 1 of 7	NP_001361014.1	A0A024R445
	BCS1L	NM_001371453.1		c.-605A>G		5_prime_UTR	Exon 2 of 8	NP_001358382.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCS1L	ENST00000359273.8	TSL:1 MANE Select	c.-49-80A>G		intron	N/A	ENSP00000352219.3	Q9Y276
	BCS1L	ENST00000392109.5	TSL:1	c.-49-80A>G		intron	N/A	ENSP00000375957.1	Q9Y276
	BCS1L	ENST00000392111.7	TSL:1	c.-49-80A>G		intron	N/A	ENSP00000375959.2	Q9Y276

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

African (AFR) AF: 0.965 AC: 21511 AN: 22298

American (AMR) AF: 0.998 AC: 38221 AN: 38292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 20782 AN: 20782

East Asian (EAS) AF: 1.00 AC: 35990 AN: 35990

South Asian (SAS) AF: 1.00 AC: 69111 AN: 69122

European-Finnish (FIN) AF: 1.00 AC: 36636 AN: 36636

Middle Eastern (MID) AF: 0.998 AC: 3163 AN: 3170

European-Non Finnish (NFE) AF: 1.00 AC: 603722 AN: 603814

Other (OTH) AF: 0.997 AC: 40762 AN: 40894

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

African (AFR) AF: 0.964 AC: 40057 AN: 41558

American (AMR) AF: 0.996 AC: 15251 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68033 AN: 68042

Other (OTH) AF: 0.995 AC: 2106 AN: 2116

Alfa AF: 0.993 Hom.: 10022

Bravo AF: 0.989

Asia WGS AF: 0.996 AC: 3462 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6722185; hg19: chr2-219525582;