19-14571992-G-C

Variant names:

• chr19-14571992-G-C
• rs9543
• NM_004146.6:c.9C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004146.6(NDUFB7):​c.9C>G​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,595,678 control chromosomes in the GnomAD database, including 215,299 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 0.57 (26271 hom., cov: 33)
  • Exomes 𝑓: 0.51 (189028 hom.)
• Consequence: NDUFB7 NM_004146.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 20 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.394 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

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.9C>G	p.Ala3Ala	synonymous	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.9C>G	p.Ala3Ala	synonymous	Exon 1 of 3	ENSP00000215565.1
	NDUFB7	ENST00000593353.5	TSL:2	n.9C>G		non_coding_transcript_exon	Exon 1 of 3	ENSP00000473120.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87047 AN: 152000 Hom.: 26225 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.555

GnomAD2 exomes AF: 0.506 AC: 109467 AN: 216544 AF XY: 0.505

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.311

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.508 AC: 732987 AN: 1443558 Hom.: 189028 Cov.: 38 AF XY: 0.508 AC XY: 364215 AN XY: 716676

African (AFR) AF: 0.795 AC: 26404 AN: 33228

American (AMR) AF: 0.426 AC: 17856 AN: 41878

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14462 AN: 25632

East Asian (EAS) AF: 0.293 AC: 11428 AN: 39004

South Asian (SAS) AF: 0.522 AC: 43832 AN: 83906

European-Finnish (FIN) AF: 0.500 AC: 25654 AN: 51326

Middle Eastern (MID) AF: 0.543 AC: 2962 AN: 5450

European-Non Finnish (NFE) AF: 0.507 AC: 559858 AN: 1103530

Other (OTH) AF: 0.512 AC: 30531 AN: 59604

GnomAD4 genome AF: 0.573 AC: 87144 AN: 152120 Hom.: 26271 Cov.: 33 AF XY: 0.567 AC XY: 42159 AN XY: 74374

African (AFR) AF: 0.781 AC: 32422 AN: 41540

American (AMR) AF: 0.464 AC: 7091 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1992 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1591 AN: 5158

South Asian (SAS) AF: 0.515 AC: 2480 AN: 4820

European-Finnish (FIN) AF: 0.500 AC: 5291 AN: 10590

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34675 AN: 67932

Other (OTH) AF: 0.552 AC: 1166 AN: 2114

Alfa AF: 0.540 Hom.: 7282

Bravo AF: 0.578

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		-0.39
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs9543; hg19: chr19-14682804; COSMIC: COSV53107728;