rs45628939

Positions:

• chr19-14572039-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004146.6(NDUFB7):​c.-39G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,477,652 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0085 (15 hom., cov: 33)
  • Exomes 𝑓: 0.010 (88 hom.)
• Consequence: NDUFB7 NM_004146.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

Genes affected

NDUFB7 (HGNC:7702): (NADH:ubiquinone oxidoreductase subunit B7) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It is located at the mitochondrial inner membrane. 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB7	NM_004146.6	c.-39G>C		5_prime_UTR_variant	1/3	ENST00000215565.3	NP_004137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFB7	ENST00000215565.3	c.-39G>C		5_prime_UTR_variant	1/3	1	NM_004146.6	ENSP00000215565	P1
NDUFB7	ENST00000593353.5	c.-39G>C		5_prime_UTR_variant, NMD_transcript_variant	1/3	2		ENSP00000473120

Frequencies

GnomAD3 genomes AF: 0.00856 AC: 1303 AN: 152242 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00875 AC: 1245 AN: 142266 Hom.: 4 AF XY: 0.00838 AC XY: 637 AN XY: 75992

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.0000842

Gnomad SAS exome AF: 0.00171

Gnomad FIN exome AF: 0.0113

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0103 AC: 13662 AN: 1325292 Hom.: 88 Cov.: 21 AF XY: 0.00998 AC XY: 6532 AN XY: 654768

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000829

Gnomad4 SAS exome AF: 0.00187

Gnomad4 FIN exome AF: 0.00990

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00854 AC: 1301 AN: 152360 Hom.: 15 Cov.: 33 AF XY: 0.00885 AC XY: 659 AN XY: 74504

Gnomad4 AFR AF: 0.00175

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00872 Hom.: 1

Bravo AF: 0.00881

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs45628939; hg19: chr19-14682851;