10-100529321-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005004.4(NDUFB8):c.212+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,498,316 control chromosomes in the GnomAD database, including 35,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3291 hom., cov: 28)
  • Exomes 𝑓: 0.22 (32251 hom.)
• Consequence: NDUFB8 NM_005004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.419

Genes affected

NDUFB8 (HGNC:7703): (NADH:ubiquinone oxidoreductase subunit B8) Involved in mitochondrial respiratory chain complex I assembly. Located in endoplasmic reticulum and mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 32. Biomarker of Alzheimer's disease and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

HIF1AN (HGNC:17113): (hypoxia inducible factor 1 subunit alpha inhibitor) Enables several functions, including 2-oxoglutarate-dependent dioxygenase activity; NF-kappaB binding activity; and transition metal ion binding activity. Involved in several processes, including negative regulation of Notch signaling pathway; negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; and protein hydroxylation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-100529321-C-A is Benign according to our data. Variant chr10-100529321-C-A is described in ClinVar as [Benign]. Clinvar id is 1268122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFB8	NM_005004.4	c.212+59G>T		intron_variant		ENST00000299166.9
NDUFB8	NM_001284367.2	c.212+59G>T		intron_variant
NDUFB8	NM_001284368.1	c.119+59G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB8	ENST00000299166.9	c.212+59G>T		intron_variant		1	NM_005004.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31074 AN: 150776 Hom.: 3286 Cov.: 28

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.217 AC: 291780 AN: 1347424 Hom.: 32251 Cov.: 30 AF XY: 0.217 AC XY: 144144 AN XY: 663572

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.206 AC: 31083 AN: 150892 Hom.: 3291 Cov.: 28 AF XY: 0.206 AC XY: 15205 AN XY: 73638

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.203

Alfa AF: 0.215 Hom.: 814

Bravo AF: 0.203

Asia WGS AF: 0.191 AC: 664 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

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.5
Dann	Benign	0.85

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: rs1800662; hg19: chr10-102289078; COSMIC: COSV54511979; COSMIC: COSV54511979;