4-139301326-T-C

Position:

• chr4-139301326-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001184989.2(NDUFC1):​c.-222+1090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 399,296 control chromosomes in the GnomAD database, including 161,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62992 hom., cov: 32)
  • Exomes 𝑓: 0.89 (98574 hom.)
• Consequence: NDUFC1 NM_001184989.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.332

Genes affected

NDUFC1 (HGNC:7705): (NADH:ubiquinone oxidoreductase subunit C1) The encoded protein is a subunit of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 4-139301326-T-C is Benign according to our data. Variant chr4-139301326-T-C is described in ClinVar as [Benign]. Clinvar id is 1263855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFC1	NM_001184989.2	c.-222+1090A>G		intron_variant		ENST00000394223.2
NDUFC1	NM_001184987.1	c.-163+1090A>G		intron_variant
NDUFC1	NM_001184988.1	c.-199+1090A>G		intron_variant
NDUFC1	NM_001184990.1	c.-159+1090A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFC1	ENST00000394223.2	c.-222+1090A>G		intron_variant		3	NM_001184989.2	P1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138194 AN: 152164 Hom.: 62932 Cov.: 32

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.892 AC: 220430 AN: 247014 Hom.: 98574 Cov.: 0 AF XY: 0.892 AC XY: 112322 AN XY: 125876

Gnomad4 AFR exome AF: 0.973

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.911

Gnomad4 FIN exome AF: 0.913

Gnomad4 NFE exome AF: 0.879

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.908 AC: 138311 AN: 152282 Hom.: 62992 Cov.: 32 AF XY: 0.912 AC XY: 67884 AN XY: 74462

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.899

Alfa AF: 0.875 Hom.: 2803

Bravo AF: 0.902

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6851954; hg19: chr4-140222480;