Genetic Variant NDUFB7:p.Ala3Ala (chr19-14571992-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.394

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB7	NM_004146.6 link	c.9C>G	p.Ala3Ala	synonymous_variant	Exon 1 of 3	ENST00000215565.3	NP_004137.2	P17568

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB7	ENST00000215565.3 link	c.9C>G	p.Ala3Ala	synonymous_variant	Exon 1 of 3	1	NM_004146.6	ENSP00000215565.1		P17568
NDUFB7	ENST00000593353.5 link	n.9C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000473120.1		M0R3B8

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87047

AN:

152000

Hom.:

26225

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.506

AC:

109467

AN:

216544

Hom.:

28338

AF XY:

0.505

AC XY:

59461

AN XY:

117726

show subpopulations

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 SAS exome

AF:

0.526

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.:

AF XY:

0.508

AC XY:

364215

AN XY:

716676

show subpopulations

Gnomad4 AFR exome

AF:

0.795

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.507

Gnomad4 OTH exome

AF:

0.512

GnomAD4 genome

AF:

0.573

AC:

87144

AN:

152120

Hom.:

26271

Cov.:

AF XY:

0.567

AC XY:

42159

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.781

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.574

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.552

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

DANN

Benign

0.64

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over