rs3763851

chr11-62804961-C-A

Variant summary

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

The NM_006362.5(NXF1):c.28+368G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 213,422 control chromosomes in the GnomAD database, including 24,260 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 0.41 (15479 hom., cov: 31)
  • Exomes 𝑓: 0.52 (8781 hom.)
• Consequence: NXF1 NM_006362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

Genes affected

NXF1 (HGNC:8071): (nuclear RNA export factor 1) This gene is one member of a family of nuclear RNA export factor genes. Common domain features of this family are a noncanonical RNP-type RNA-binding domain (RBD), 4 leucine-rich repeats (LRRs), a nuclear transport factor 2 (NTF2)-like domain that allows heterodimerization with NTF2-related export protein-1 (NXT1), and a ubiquitin-associated domain that mediates interactions with nucleoporins. The LRRs and NTF2-like domains are required for export activity. Alternative splicing seems to be a common mechanism in this gene family. The encoded protein of this gene shuttles between the nucleus and the cytoplasm and binds in vivo to poly(A)+ RNA. It is the vertebrate homologue of the yeast protein Mex67p. The encoded protein overcomes the mRNA export block caused by the presence of saturating amounts of CTE (constitutive transport element) RNA of type D retroviruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF1	NM_006362.5	c.28+368G>T		intron_variant		ENST00000294172.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF1	ENST00000294172.7	c.28+368G>T		intron_variant		1	NM_006362.5	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62315 AN: 151850 Hom.: 15483 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.519 AC: 31919 AN: 61454 Hom.: 8781 AF XY: 0.518 AC XY: 16070 AN XY: 30998

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.410 AC: 62312 AN: 151968 Hom.: 15479 Cov.: 31 AF XY: 0.403 AC XY: 29914 AN XY: 74274

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.458

Alfa AF: 0.500 Hom.: 11292

Bravo AF: 0.393

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	3.1
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3763851; hg19: chr11-62572433;