rs2514013

Variant names:

• chr11-67606685-A-G
• rs2514013
• ENST00000647561.1:c.-320A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-67606685-A-G
• chr11-67606685-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000647561.1(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 ENST00000647561.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.924
• Publications: 1 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]

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

ENSG00000255119 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.22T>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV1	ENST00000647561.1		c.-320A>G		5_prime_UTR	Exon 2 of 11	ENSP00000497587.1	P49821-1
	NDUFV1-DT	ENST00000333139.3	TSL:2	n.22T>C		non_coding_transcript_exon	Exon 1 of 3
	NDUFV1-DT	ENST00000810663.1		n.82T>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.851 AC: 7446 AN: 8746

American (AMR) AF: 0.987 AC: 13716 AN: 13900

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 8995 AN: 8996

East Asian (EAS) AF: 1.00 AC: 17539 AN: 17540

South Asian (SAS) AF: 1.00 AC: 42207 AN: 42226

European-Finnish (FIN) AF: 1.00 AC: 16967 AN: 16968

Middle Eastern (MID) AF: 0.983 AC: 1205 AN: 1226

European-Non Finnish (NFE) AF: 0.999 AC: 175773 AN: 175968

Other (OTH) AF: 0.988 AC: 16963 AN: 17176

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

African (AFR) AF: 0.854 AC: 35411 AN: 41442

American (AMR) AF: 0.978 AC: 14955 AN: 15296

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5058 AN: 5058

South Asian (SAS) AF: 0.999 AC: 4816 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10592 AN: 10592

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67917 AN: 68018

Other (OTH) AF: 0.964 AC: 2037 AN: 2114

Alfa AF: 0.980 Hom.: 154775

Bravo AF: 0.951

Asia WGS AF: 0.993 AC: 3454 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		-0.92
PromoterAI		-0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2514013; hg19: chr11-67374156;