Variant chr10-100529321-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.419

Variant links:

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]

NDUFB8 links:

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]

HIF1AN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NDUFB8	NM_005004.4 linkuse as main transcript	c.212+59G>T	intron_variant	ENST00000299166.9
NDUFB8	NM_001284367.2 linkuse as main transcript	c.212+59G>T	intron_variant
NDUFB8	NM_001284368.1 linkuse as main transcript	c.119+59G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFB8	ENST00000299166.9 linkuse as main transcript	c.212+59G>T		intron_variant		1	NM_005004.4	P1	O95169-1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31074

AN:

150776

Hom.:

3286

Cov.:

show subpopulations

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.:

AF XY:

0.217

AC XY:

144144

AN XY:

663572

show subpopulations

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.:

AF XY:

0.206

AC XY:

15205

AN XY:

73638

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over