Variant 10-100529731-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005004.4(NDUFB8):c.85+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,601,534 control chromosomes in the GnomAD database, including 265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 38 hom., cov: 32)

Exomes 𝑓: 0.011 ( 227 hom. )

Consequence

NDUFB8
NM_005004.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.945

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 -16 ACMG points.

BP6

Variant 10-100529731-C-T is Benign according to our data. Variant chr10-100529731-C-T is described in ClinVar as [Benign]. Clinvar id is 1264789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NDUFB8	NM_005004.4 linkuse as main transcript	c.85+36G>A	intron_variant	ENST00000299166.9	NP_004995.1
NDUFB8	NM_001284367.2 linkuse as main transcript	c.85+36G>A	intron_variant		NP_001271296.1
NDUFB8	NM_001284368.1 linkuse as main transcript	c.-9+127G>A	intron_variant		NP_001271297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB8	ENST00000299166.9 linkuse as main transcript	c.85+36G>A		intron_variant		1	NM_005004.4	ENSP00000299166	P1	O95169-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1822

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00999

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0175

AC:

4233

AN:

242078

Hom.:

109

AF XY:

0.0146

AC XY:

1914

AN XY:

131526

show subpopulations

Gnomad AFR exome

AF:

0.00244

Gnomad AMR exome

AF:

0.0780

Gnomad ASJ exome

AF:

0.00186

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00507

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.00894

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0111

AC:

16156

AN:

1449214

Hom.:

227

Cov.:

AF XY:

0.0106

AC XY:

7651

AN XY:

720160

show subpopulations

Gnomad4 AFR exome

AF:

0.00187

Gnomad4 AMR exome

AF:

0.0775

Gnomad4 ASJ exome

AF:

0.00225

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00528

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.00951

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0120

AC:

1829

AN:

152320

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

989

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.0533

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.00999

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00580

Hom.:

Bravo

AF:

0.0159

Asia WGS

AF:

0.00433

AC:

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	clinical testing	GeneDx	May 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.49

Position offset: -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