11-67606525-C-CT

Variant names:

• chr11-67606525-C-CT
• rs200876962
• ENST00000647561.1:c.-479dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000647561.1(NDUFV1):​c.-479dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 228,450 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 31)
  • Exomes 𝑓: 0.012 (14 hom.)
• Consequence: NDUFV1 ENST00000647561.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.285
• Publications: 0 publications found

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]

ENSG00000255119 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-67606525-C-CT is Benign according to our data. Variant chr11-67606525-C-CT is described in ClinVar as Likely_benign. ClinVar VariationId is 1195099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0113 (1717/152202) while in subpopulation NFE AF = 0.0174 (1184/67998). AF 95% confidence interval is 0.0166. There are 12 homozygotes in GnomAd4. There are 790 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647561.1. 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
	NDUFV1-DT	NR_130935.1		n.88+93dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV1	ENST00000647561.1		c.-479dupT		5_prime_UTR	Exon 2 of 11	ENSP00000497587.1	P49821-1
	ENSG00000255119	ENST00000533876.1	TSL:4	n.439dupT		non_coding_transcript_exon	Exon 2 of 2
	NDUFV1-DT	ENST00000333139.3	TSL:2	n.88+93dupA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1718 AN: 152084 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00905

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0120 AC: 912 AN: 76248 Hom.: 14 Cov.: 0 AF XY: 0.0114 AC XY: 463 AN XY: 40678

African (AFR) AF: 0.00183 AC: 3 AN: 1640

American (AMR) AF: 0.00996 AC: 42 AN: 4218

Ashkenazi Jewish (ASJ) AF: 0.00632 AC: 9 AN: 1424

East Asian (EAS) AF: 0.00 AC: 0 AN: 3784

South Asian (SAS) AF: 0.00881 AC: 117 AN: 13280

European-Finnish (FIN) AF: 0.00734 AC: 25 AN: 3404

Middle Eastern (MID) AF: 0.0118 AC: 3 AN: 254

European-Non Finnish (NFE) AF: 0.0149 AC: 661 AN: 44324

Other (OTH) AF: 0.0133 AC: 52 AN: 3920

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152202 Hom.: 12 Cov.: 31 AF XY: 0.0106 AC XY: 790 AN XY: 74414

African (AFR) AF: 0.00277 AC: 115 AN: 41562

American (AMR) AF: 0.0101 AC: 154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4822

European-Finnish (FIN) AF: 0.00905 AC: 96 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1184 AN: 67998

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.0122 Hom.: 3

Bravo AF: 0.0116

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs200876962; hg19: chr11-67373996;