chr5-53662727-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002495.4(NDUFS4):​c.424+4103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,794 control chromosomes in the GnomAD database, including 3,638 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 0.20 ( 3638 hom., cov: 31)

Consequence

NDUFS4
NM_002495.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.171
Variant links:
Genes affected
NDUFS4 (HGNC:7711): (NADH:ubiquinone oxidoreductase subunit S4) This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDUFS4NM_002495.4 linkuse as main transcriptc.424+4103G>A intron_variant ENST00000296684.10 NP_002486.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDUFS4ENST00000296684.10 linkuse as main transcriptc.424+4103G>A intron_variant 1 NM_002495.4 ENSP00000296684 P1

Frequencies

GnomAD3 genomes
AF:
0.203
AC:
30796
AN:
151676
Hom.:
3639
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.287
Gnomad AMI
AF:
0.0571
Gnomad AMR
AF:
0.194
Gnomad ASJ
AF:
0.179
Gnomad EAS
AF:
0.465
Gnomad SAS
AF:
0.263
Gnomad FIN
AF:
0.135
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.143
Gnomad OTH
AF:
0.209
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.203
AC:
30811
AN:
151794
Hom.:
3638
Cov.:
31
AF XY:
0.205
AC XY:
15235
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.287
Gnomad4 AMR
AF:
0.194
Gnomad4 ASJ
AF:
0.179
Gnomad4 EAS
AF:
0.465
Gnomad4 SAS
AF:
0.263
Gnomad4 FIN
AF:
0.135
Gnomad4 NFE
AF:
0.143
Gnomad4 OTH
AF:
0.211
Alfa
AF:
0.172
Hom.:
325
Bravo
AF:
0.212
Asia WGS
AF:
0.334
AC:
1158
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.8
DANN
Benign
0.26

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.

Other links and lift over

dbSNP: rs189848; hg19: chr5-52958557; API