4-139301383-A-G

Position:

• chr4-139301383-A-G

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+1033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 418,300 control chromosomes in the GnomAD database, including 13,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5691 hom., cov: 32)
  • Exomes 𝑓: 0.23 (7674 hom.)
• Consequence: NDUFC1 NM_001184989.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.756

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=-0.75).
• BP6: Variant 4-139301383-A-G is Benign according to our data. Variant chr4-139301383-A-G is described in ClinVar as [Benign]. Clinvar id is 1182664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFC1	NM_001184989.2	c.-222+1033T>C		intron_variant		ENST00000394223.2
NDUFC1	NM_001184987.1	c.-163+1033T>C		intron_variant
NDUFC1	NM_001184988.1	c.-199+1033T>C		intron_variant
NDUFC1	NM_001184990.1	c.-159+1033T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFC1	ENST00000394223.2	c.-222+1033T>C		intron_variant		3	NM_001184989.2	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40350 AN: 152000 Hom.: 5672 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.234 AC: 62176 AN: 266182 Hom.: 7674 Cov.: 0 AF XY: 0.232 AC XY: 31771 AN XY: 136658

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.266 AC: 40409 AN: 152118 Hom.: 5691 Cov.: 32 AF XY: 0.261 AC XY: 19442 AN XY: 74400

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.259

Alfa AF: 0.205 Hom.: 1049

Bravo AF: 0.267

Asia WGS AF: 0.215 AC: 749 AN: 3478

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	-0.75
CADD	Benign	5.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3806765; hg19: chr4-140222537;