rs3763851

Variant names:

• chr11-62804961-C-A
• rs3763851
• NM_006362.5:c.28+368G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000294172.7(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 ENST00000294172.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000294172.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXF1	NM_006362.5	MANE Select	c.28+368G>T		intron	N/A	NP_006353.2
	NXF1	NM_001081491.2		c.28+368G>T		intron	N/A	NP_001074960.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXF1	ENST00000294172.7	TSL:1 MANE Select	c.28+368G>T		intron	N/A	ENSP00000294172.2
	NXF1	ENST00000530875.5	TSL:1	c.28+368G>T		intron	N/A	ENSP00000435742.1
	NXF1	ENST00000531709.6	TSL:1	c.28+368G>T		intron	N/A	ENSP00000453885.1

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

African (AFR) AF: 0.137 AC: 276 AN: 2012

American (AMR) AF: 0.327 AC: 510 AN: 1558

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1289 AN: 2396

East Asian (EAS) AF: 0.415 AC: 1795 AN: 4326

South Asian (SAS) AF: 0.264 AC: 282 AN: 1068

European-Finnish (FIN) AF: 0.506 AC: 2349 AN: 4638

Middle Eastern (MID) AF: 0.470 AC: 154 AN: 328

European-Non Finnish (NFE) AF: 0.567 AC: 23168 AN: 40828

Other (OTH) AF: 0.487 AC: 2096 AN: 4300

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

African (AFR) AF: 0.133 AC: 5515 AN: 41466

American (AMR) AF: 0.376 AC: 5736 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2040 AN: 5168

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4814

European-Finnish (FIN) AF: 0.480 AC: 5065 AN: 10544

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38911 AN: 67924

Other (OTH) AF: 0.458 AC: 966 AN: 2108

Alfa AF: 0.495 Hom.: 15550

Bravo AF: 0.393

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.1
DANN	Benign	0.82
PhyloP100		-0.36
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3763851; hg19: chr11-62572433;