rs2288414

Positions:

• chr19-8320768-C-G
• chr19-8320768-C-T

Variant summary

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

The NM_005001.5(NDUFA7):​c.101+89G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,502,462 control chromosomes in the GnomAD database, including 6,006 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 0.13 (2798 hom., cov: 32)
  • Exomes 𝑓: 0.045 (3208 hom.)
• Consequence: NDUFA7 NM_005001.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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]

ENSG00000167774 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA7	NM_005001.5	c.101+89G>C		intron_variant		ENST00000301457.3	NP_004992.2
NDUFA7	NR_135539.2	n.118+89G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3	c.101+89G>C		intron_variant		1	NM_005001.5	ENSP00000301457.1
ENSG00000167774	ENST00000598884.1	n.101+89G>C		intron_variant		4		ENSP00000470609.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19760 AN: 152042 Hom.: 2780 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0449 AC: 60688 AN: 1350302 Hom.: 3208 AF XY: 0.0436 AC XY: 29429 AN XY: 674820

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.0501

Gnomad4 ASJ exome AF: 0.0605

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.0346

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0341

Gnomad4 OTH exome AF: 0.0619

GnomAD4 genome AF: 0.130 AC: 19816 AN: 152160 Hom.: 2798 Cov.: 32 AF XY: 0.129 AC XY: 9597 AN XY: 74388

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0850 Hom.: 185

Bravo AF: 0.144

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.50

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: rs2288414; hg19: chr19-8385652;