rs1800649

Variant names:

• chr2-97648394-C-A
• rs1800649
• NM_001862.3:c.*286C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-97648394-C-A
• chr2-97648394-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001862.3(COX5B):​c.*286C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COX5B NM_001862.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 15 publications found

Genes affected

COX5B (HGNC:2269): (cytochrome c oxidase subunit 5B) Cytochrome C oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit Vb of the human mitochondrial respiratory chain enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX5B	NM_001862.3	MANE Select	c.*286C>A		downstream_gene	N/A	NP_001853.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX5B	ENST00000258424.3	TSL:1 MANE Select	c.*286C>A		downstream_gene	N/A	ENSP00000258424.2
	COX5B	ENST00000464949.5	TSL:5	n.*203C>A		downstream_gene	N/A
	COX5B	ENST00000491989.1	TSL:3	n.*215C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 175240 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 89114

African (AFR) AF: 0.00 AC: 0 AN: 4674

American (AMR) AF: 0.00 AC: 0 AN: 4232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6524

East Asian (EAS) AF: 0.00 AC: 0 AN: 12036

South Asian (SAS) AF: 0.00 AC: 0 AN: 8426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 952

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 114930

Other (OTH) AF: 0.00 AC: 0 AN: 11668

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.16
DANN	Benign	0.55
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs1800649; hg19: chr2-98264857;