11-67606685-A-G

Variant names:

• chr11-67606685-A-G
• rs2514013
• ENST00000647561:c.-320A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000647561(NDUFV1):​c.-320A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 454,762 control chromosomes in the GnomAD database, including 219,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69914 hom., cov: 29)
  • Exomes 𝑓: 0.99 (149561 hom.)
• Consequence: NDUFV1 ENST00000647561 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.924

Genes affected

NDUFV1 (HGNC:7716): (NADH:ubiquinone oxidoreductase core subunit V1) The mitochondrial respiratory chain provides energy to cells via oxidative phosphorylation and consists of four membrane-bound electron-transporting protein complexes (I-IV) and an ATP synthase (complex V). This gene encodes a 51 kDa subunit of the NADH:ubiquinone oxidoreductase complex I; a large complex with at least 45 nuclear and mitochondrial encoded subunits that liberates electrons from NADH and channels them to ubiquinone. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-biding sites. Defects in complex I are a common cause of mitochondrial dysfunction; a syndrome that occurs in approximately 1 in 10,000 live births. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

NDUFV1-DT (HGNC:26915): (NDUFV1 divergent transcript)

ENSG00000255119 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-67606685-A-G is Benign according to our data. Variant chr11-67606685-A-G is described in ClinVar as [Benign]. Clinvar id is 683144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV1-DT	NR_130935.1	n.22T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFV1	ENST00000647561	c.-320A>G		5_prime_UTR_variant	Exon 2 of 11			ENSP00000497587.1
NDUFV1-DT	ENST00000333139.3	n.22T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
NDUFV1	ENST00000532303.5	c.-540A>G		upstream_gene_variant		2		ENSP00000432015.1

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145337 AN: 151898 Hom.: 69866 Cov.: 29

Gnomad AFR AF: 0.854

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 0.994 AC: 300811 AN: 302746 Hom.: 149561 Cov.: 2 AF XY: 0.995 AC XY: 159499 AN XY: 160352

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.988

GnomAD4 genome AF: 0.957 AC: 145445 AN: 152016 Hom.: 69914 Cov.: 29 AF XY: 0.959 AC XY: 71189 AN XY: 74268

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.964

Alfa AF: 0.993 Hom.: 99338

Bravo AF: 0.951

Asia WGS AF: 0.993 AC: 3454 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2514013; hg19: chr11-67374156;