Genetic Variant NDUFB2:p.Asp28Glu (chr7-140696828-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004546.3(NDUFB2):c.84T>G(p.Asp28Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,455,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D28N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NDUFB2
NM_004546.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.217

Publications

0 publications found

Variant links:

Genes affected

NDUFB2 (HGNC:7697): (NADH:ubiquinone oxidoreductase subunit B2) 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. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays a important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Hydropathy analysis revealed that this subunit and 4 other subunits have an overall hydrophilic pattern, even though they are found within the hydrophobic protein (HP) fraction of complex I. [provided by RefSeq, Jul 2008]

NDUFB2 links:

NDUFB2-AS1 (HGNC:40396): (NDUFB2 antisense RNA 1)

NDUFB2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046247333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004546.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB2	NM_004546.3	MANE Select	c.84T>G	p.Asp28Glu	missense	Exon 1 of 4	NP_004537.1	O95178
	NDUFB2-AS1	NR_024454.1		n.164-8A>C		splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDUFB2	ENST00000247866.9	TSL:1 MANE Select	c.84T>G	p.Asp28Glu	missense	Exon 1 of 4	ENSP00000247866.4	O95178
NDUFB2	ENST00000465506.5	TSL:1	c.84T>G	p.Asp28Glu	missense	Exon 1 of 3	ENSP00000419357.1	O95178
NDUFB2	ENST00000476181.5	TSL:1	n.84T>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000418347.1	F8WCJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

236390

AF XY:

0.00000778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1455718

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

723744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39310

South Asian (SAS)

AF:

0.00

AC:

AN:

85200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1109502

Other (OTH)

AF:

0.00

AC:

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000826

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.6

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.32

M_CAP

Benign

0.0027

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

-0.22

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.37

REVEL

Benign

0.014

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MutPred

0.24

Gain of helix (P = 0.0854)

MVP

0.26

MPC

0.25

ClinPred

0.016

GERP RS

1.2

PromoterAI

-0.30

Neutral

(source)

Varity_R

0.033

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over