NM_005004.4:c.85+36G>A

Variant names:

• chr10-100529731-C-T
• rs181643313
• NM_005004.4:c.85+36G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.945
• Publications: 1 publications found

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]

ENSG00000255339 (HGNC:):

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005004.4. 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
	NDUFB8	NM_005004.4	MANE Select	c.85+36G>A		intron	N/A	NP_004995.1	O95169-1
	NDUFB8	NM_001284367.2		c.85+36G>A		intron	N/A	NP_001271296.1	O95169-2
	NDUFB8	NM_001284368.1		c.-9+127G>A		intron	N/A	NP_001271297.1	O95169-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB8	ENST00000299166.9	TSL:1 MANE Select	c.85+36G>A		intron	N/A	ENSP00000299166.4	O95169-1
	ENSG00000255339	ENST00000557395.5	TSL:2	n.85+36G>A		intron	N/A	ENSP00000456832.1
	NDUFB8	ENST00000937696.1		c.85+36G>A		intron	N/A	ENSP00000607755.1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1822 AN: 152202 Hom.: 38 Cov.: 32

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

GnomAD2 exomes AF: 0.0175 AC: 4233 AN: 242078 AF XY: 0.0146

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 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.: 31 AF XY: 0.0106 AC XY: 7651 AN XY: 720160

African (AFR) AF: 0.00187 AC: 62 AN: 33144

American (AMR) AF: 0.0775 AC: 3344 AN: 43146

Ashkenazi Jewish (ASJ) AF: 0.00225 AC: 58 AN: 25736

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39420

South Asian (SAS) AF: 0.00528 AC: 451 AN: 85346

European-Finnish (FIN) AF: 0.0209 AC: 1066 AN: 51086

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5728

European-Non Finnish (NFE) AF: 0.00951 AC: 10516 AN: 1105712

Other (OTH) AF: 0.0108 AC: 648 AN: 59896

GnomAD4 genome AF: 0.0120 AC: 1829 AN: 152320 Hom.: 38 Cov.: 32 AF XY: 0.0133 AC XY: 989 AN XY: 74470

African (AFR) AF: 0.00204 AC: 85 AN: 41578

American (AMR) AF: 0.0533 AC: 815 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4830

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00999 AC: 680 AN: 68042

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00580 Hom.: 3

Bravo AF: 0.0159

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		0.94
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs181643313; hg19: chr10-102289488;