rs3826777

chr19-49928131-G-Achr19-49928131-G-C

Variant summary

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

The NM_016553.5(NUP62):c.-199-316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,132 control chromosomes in the GnomAD database, including 9,190 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 0.34 (9188 hom., cov: 31)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: NUP62 NM_016553.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

NUP62 (HGNC:8066): (nucleoporin 62) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]

IL4I1 (HGNC:19094): (interleukin 4 induced 1) This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP62	NM_016553.5	c.-199-316C>T		intron_variant		ENST00000352066.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP62	ENST00000352066.8	c.-199-316C>T		intron_variant		1	NM_016553.5	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51799 AN: 151944 Hom.: 9189 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.271 AC: 19 AN: 70 Hom.: 2 Cov.: 0 AF XY: 0.260 AC XY: 13 AN XY: 50

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.341 AC: 51814 AN: 152062 Hom.: 9188 Cov.: 31 AF XY: 0.345 AC XY: 25634 AN XY: 74342

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.348

Alfa AF: 0.358 Hom.: 4705

Bravo AF: 0.336

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.5
Dann	Benign	0.70

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: rs3826777; hg19: chr19-50431388; COSMIC: COSV61311459; COSMIC: COSV61311459;