19-14572039-C-G

Variant names:

• chr19-14572039-C-G
• rs45628939
• NM_004146.6:c.-39G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

NDUFB7 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 39

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004146.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	NM_004146.6	MANE Select	c.-39G>C		5_prime_UTR	Exon 1 of 3	NP_004137.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	ENST00000215565.3	TSL:1 MANE Select	c.-39G>C		5_prime_UTR	Exon 1 of 3	ENSP00000215565.1
	NDUFB7	ENST00000593353.5	TSL:2	n.-39G>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000473120.1
	NDUFB7	ENST00000593353.5	TSL:2	n.-39G>C		5_prime_UTR	Exon 1 of 3	ENSP00000473120.1

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

GnomAD2 exomes AF: 0.00875 AC: 1245 AN: 142266 AF XY: 0.00838

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 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

African (AFR) AF: 0.00147 AC: 44 AN: 30018

American (AMR) AF: 0.0105 AC: 356 AN: 33798

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 253 AN: 23090

East Asian (EAS) AF: 0.0000829 AC: 3 AN: 36182

South Asian (SAS) AF: 0.00187 AC: 143 AN: 76356

European-Finnish (FIN) AF: 0.00990 AC: 462 AN: 46668

Middle Eastern (MID) AF: 0.00778 AC: 40 AN: 5144

European-Non Finnish (NFE) AF: 0.0116 AC: 11800 AN: 1018874

Other (OTH) AF: 0.0102 AC: 561 AN: 55162

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

African (AFR) AF: 0.00175 AC: 73 AN: 41600

American (AMR) AF: 0.0163 AC: 250 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		2.6
PromoterAI		0.29	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs45628939; hg19: chr19-14682851;