rs2333686

Positions:

• chr1-183596965-C-T

Variant summary

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

The XM_047421222.1(NCF2):​c.-143-4399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,066 control chromosomes in the GnomAD database, including 11,650 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 0.39 (11650 hom., cov: 32)
• Consequence: NCF2 XM_047421222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

Genes affected

NCF2 (HGNC:):

SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCF2	XM_047421222.1	c.-143-4399G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG7	ENST00000495321.1	n.234-804C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59024 AN: 151948 Hom.: 11625 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.389 AC: 59082 AN: 152066 Hom.: 11650 Cov.: 32 AF XY: 0.384 AC XY: 28569 AN XY: 74318

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.382

Alfa AF: 0.394 Hom.: 3620

Bravo AF: 0.389

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2333686; hg19: chr1-183566100;