4-139301217-G-A

Position:

• chr4-139301217-G-A

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+1199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 262,840 control chromosomes in the GnomAD database, including 3,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1772 hom., cov: 33)
  • Exomes 𝑓: 0.16 (1632 hom.)
• Consequence: NDUFC1 NM_001184989.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.64

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 4-139301217-G-A is Benign according to our data. Variant chr4-139301217-G-A is described in ClinVar as [Benign]. Clinvar id is 1265947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFC1	NM_001184989.2	c.-222+1199C>T		intron_variant		ENST00000394223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFC1	ENST00000394223.2	c.-222+1199C>T		intron_variant		3	NM_001184989.2	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20917 AN: 152178 Hom.: 1773 Cov.: 33

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.159 AC: 17554 AN: 110544 Hom.: 1632 Cov.: 0 AF XY: 0.160 AC XY: 8783 AN XY: 54952

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.0417

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.137 AC: 20915 AN: 152296 Hom.: 1772 Cov.: 33 AF XY: 0.137 AC XY: 10205 AN XY: 74452

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.146

Alfa AF: 0.156 Hom.: 239

Bravo AF: 0.128

Asia WGS AF: 0.106 AC: 371 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	-0.77
CADD	Benign	14
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3806766; hg19: chr4-140222371;