18-9109486-T-G

Variant names:

• chr18-9109486-T-G
• rs4148965
• NM_021074.5:c.54+6689T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021074.5(NDUFV2):​c.54+6689T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,108 control chromosomes in the GnomAD database, including 30,678 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 0.62 (30678 hom., cov: 32)
• Consequence: NDUFV2 NM_021074.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

NDUFV2 (HGNC:7717): (NADH:ubiquinone oxidoreductase core subunit V2) The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes the 24 kDa subunit of complex I, and is involved in electron transfer. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy. A non-transcribed pseudogene of this locus is found on chromosome 19. [provided by RefSeq, Oct 2009]

ENSG00000265257 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV2	NM_021074.5	c.54+6689T>G		intron_variant	Intron 1 of 7	ENST00000318388.11	NP_066552.2
NDUFV2	XR_243808.4	n.99+6689T>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFV2	ENST00000318388.11	c.54+6689T>G		intron_variant	Intron 1 of 7	1	NM_021074.5	ENSP00000327268.6

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94616 AN: 151990 Hom.: 30668 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.654

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94659 AN: 152108 Hom.: 30678 Cov.: 32 AF XY: 0.627 AC XY: 46646 AN XY: 74374

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.650

Alfa AF: 0.686 Hom.: 47339

Bravo AF: 0.611

Asia WGS AF: 0.648 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4148965; hg19: chr18-9109484;