rs7789764

Variant names:

• chr7-10933735-C-T
• rs7789764
• NM_002489.4:c.190-43G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002489.4(COXFA4):​c.190-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,397,916 control chromosomes in the GnomAD database, including 241,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (34146 hom., cov: 32)
  • Exomes 𝑓: 0.57 (207784 hom.)
• Consequence: COXFA4 NM_002489.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 6 publications found

Genes affected

COXFA4 (HGNC:7687): (NDUFA4 mitochondrial complex associated) The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

COXFA4 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• Leigh syndrome with leukodystrophy

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

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-10933735-C-T is Benign according to our data. Variant chr7-10933735-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002489.4. 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
	COXFA4	NM_002489.4	MANE Select	c.190-43G>A		intron	N/A	NP_002480.1	O00483

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA4	ENST00000339600.6	TSL:1 MANE Select	c.190-43G>A		intron	N/A	ENSP00000339720.5	O00483
	NDUFA4	ENST00000855674.1		c.190-43G>A		intron	N/A	ENSP00000525733.1
	NDUFA4	ENST00000923092.1		c.190-43G>A		intron	N/A	ENSP00000593151.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99516 AN: 151922 Hom.: 34070 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.633

GnomAD2 exomes AF: 0.611 AC: 146508 AN: 239874 AF XY: 0.608

Gnomad AFR exome AF: 0.871

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.698

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.573 AC: 713646 AN: 1245878 Hom.: 207784 Cov.: 17 AF XY: 0.576 AC XY: 363109 AN XY: 630684

African (AFR) AF: 0.872 AC: 25484 AN: 29226

American (AMR) AF: 0.587 AC: 25925 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 15675 AN: 24774

East Asian (EAS) AF: 0.715 AC: 27533 AN: 38494

South Asian (SAS) AF: 0.671 AC: 54708 AN: 81554

European-Finnish (FIN) AF: 0.583 AC: 28531 AN: 48944

Middle Eastern (MID) AF: 0.692 AC: 3701 AN: 5346

European-Non Finnish (NFE) AF: 0.544 AC: 500233 AN: 919948

Other (OTH) AF: 0.596 AC: 31856 AN: 53416

GnomAD4 genome AF: 0.655 AC: 99656 AN: 152038 Hom.: 34146 Cov.: 32 AF XY: 0.660 AC XY: 49026 AN XY: 74312

African (AFR) AF: 0.865 AC: 35871 AN: 41486

American (AMR) AF: 0.583 AC: 8920 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2200 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3622 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6342 AN: 10540

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37341 AN: 67948

Other (OTH) AF: 0.638 AC: 1346 AN: 2110

Alfa AF: 0.584 Hom.: 34452

Bravo AF: 0.660

Asia WGS AF: 0.703 AC: 2440 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.071
DANN	Benign	0.62
PhyloP100		-1.3
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: rs7789764; hg19: chr7-10973362;