rs2232765

Positions:

• chr19-8309181-G-C
• chr19-8309181-G-T

Variant summary

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

The ENST00000593729.5(NDUFA7):​c.*94-297C>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,574 control chromosomes in the GnomAD database, including 13,133 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 0.41 (13133 hom., cov: 31)
• Consequence: NDUFA7 ENST00000593729.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA7	NR_135539.2	n.453-297C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA7	ENST00000593729.5	c.*94-297C>G		intron_variant, NMD_transcript_variant		2
NDUFA7	ENST00000595856.5	c.*299-297C>G		intron_variant, NMD_transcript_variant		5
NDUFA7	ENST00000601101.5	c.*94-297C>G		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62435 AN: 151456 Hom.: 13107 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.412 AC: 62509 AN: 151574 Hom.: 13133 Cov.: 31 AF XY: 0.418 AC XY: 30937 AN XY: 74024

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.375

Alfa AF: 0.396 Hom.: 1448

Bravo AF: 0.405

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.42

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: rs2232765; hg19: chr19-8374065;