Genetic Variant NDUFA4:c.190-43G>A (chr7-10933735-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002489.4(NDUFA4):c.190-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,397,916 control chromosomes in the GnomAD database, including 241,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.66 ( 34146 hom., cov: 32)

Exomes 𝑓: 0.57 ( 207784 hom. )

Consequence

NDUFA4
NM_002489.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

Variant links:

Genes affected

NDUFA4 (HGNC:7687): (NDUFA4 mitochondrial complex associated) The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. 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]

NDUFA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-10933735-C-T is Benign according to our data. Variant chr7-10933735-C-T is described in ClinVar as [Benign]. Clinvar id is 1291023.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA4	NM_002489.4 link	c.190-43G>A		intron_variant	Intron 3 of 3	ENST00000339600.6	NP_002480.1	O00483A0A024R9Z0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NDUFA4	ENST00000339600.6 link	c.190-43G>A	intron_variant	Intron 3 of 3	1	NM_002489.4	ENSP00000339720.5	O00483
NDUFA4	ENST00000470761.5 link	n.475-43G>A	intron_variant	Intron 3 of 3	4
NDUFA4	ENST00000482299.1 link	n.429-43G>A	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99516

AN:

151922

Hom.:

34070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.864

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.633

GnomAD3 exomes

AF:

0.611

AC:

146508

AN:

239874

Hom.:

45533

AF XY:

0.608

AC XY:

79207

AN XY:

130236

show subpopulations

Gnomad AFR exome

AF:

0.871

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.632

Gnomad EAS exome

AF:

0.698

Gnomad SAS exome

AF:

0.674

Gnomad FIN exome

AF:

0.586

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.573

AC:

713646

AN:

1245878

Hom.:

207784

Cov.:

AF XY:

0.576

AC XY:

363109

AN XY:

630684

show subpopulations

Gnomad4 AFR exome

AF:

0.872

Gnomad4 AMR exome

AF:

0.587

Gnomad4 ASJ exome

AF:

0.633

Gnomad4 EAS exome

AF:

0.715

Gnomad4 SAS exome

AF:

0.671

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.655

AC:

99656

AN:

152038

Hom.:

34146

Cov.:

AF XY:

0.660

AC XY:

49026

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.865

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.700

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.575

Hom.:

26271

Bravo

AF:

0.660

Asia WGS

AF:

0.703

AC:

2440

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.071

DANN

Benign

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over