2-97646107-C-T

Variant names:

• chr2-97646107-C-T
• rs114574573
• NM_001862.3:c.21C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001862.3(COX5B):​c.21C>T​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 1,556,448 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (66 hom.)
• Consequence: COX5B NM_001862.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.954

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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 2-97646107-C-T is Benign according to our data. Variant chr2-97646107-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.954 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX5B	NM_001862.3	c.21C>T	p.Arg7Arg	synonymous_variant	Exon 1 of 4	ENST00000258424.3	NP_001853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX5B	ENST00000258424.3	c.21C>T	p.Arg7Arg	synonymous_variant	Exon 1 of 4	1	NM_001862.3	ENSP00000258424.2
COX5B	ENST00000464949.5	n.11C>T		non_coding_transcript_exon_variant	Exon 1 of 5	5
COX5B	ENST00000491989.1	n.-182C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 723 AN: 152224 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00430 AC: 689 AN: 160278 AF XY: 0.00464

Gnomad AFR exome AF: 0.00164

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00897

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00857 AC: 12040 AN: 1404106 Hom.: 66 Cov.: 30 AF XY: 0.00846 AC XY: 5863 AN XY: 693128

Gnomad4 AFR exome AF: 0.00172 AC: 55 AN: 31884

Gnomad4 AMR exome AF: 0.00211 AC: 77 AN: 36462

Gnomad4 ASJ exome AF: 0.00123 AC: 31 AN: 25202

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 36146

Gnomad4 SAS exome AF: 0.000314 AC: 25 AN: 79602

Gnomad4 FIN exome AF: 0.000589 AC: 29 AN: 49256

Gnomad4 NFE exome AF: 0.0104 AC: 11260 AN: 1081674

Gnomad4 Remaining exome AF: 0.00911 AC: 530 AN: 58178

GnomAD4 genome AF: 0.00475 AC: 723 AN: 152342 Hom.: 3 Cov.: 32 AF XY: 0.00436 AC XY: 325 AN XY: 74492

Gnomad4 AFR AF: 0.00178 AC: 0.00177945 AN: 0.00177945

Gnomad4 AMR AF: 0.00268 AC: 0.00267729 AN: 0.00267729

Gnomad4 ASJ AF: 0.00144 AC: 0.00144009 AN: 0.00144009

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207039 AN: 0.000207039

Gnomad4 FIN AF: 0.000188 AC: 0.000188395 AN: 0.000188395

Gnomad4 NFE AF: 0.00872 AC: 0.008717 AN: 0.008717

Gnomad4 OTH AF: 0.00284 AC: 0.00283554 AN: 0.00283554

Alfa AF: 0.00649 Hom.: 3

Bravo AF: 0.00490

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

COX5B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	12
DANN	Benign	0.95
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

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: rs114574573; hg19: chr2-98262570; COSMIC: COSV99300348; COSMIC: COSV99300348;