chr19-49908290-G-A

Position:

• chr19-49908290-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_016553.5(NUP62):​c.1518C>T​(p.Cys506Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,613,882 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (14 hom.)
• Consequence: NUP62 NM_016553.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.177

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]

IL4I1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 19-49908290-G-A is Benign according to our data. Variant chr19-49908290-G-A is described in ClinVar as [Benign]. Clinvar id is 719935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49908290-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP62	NM_016553.5	c.1518C>T	p.Cys506Cys	synonymous_variant	3/3	ENST00000352066.8	NP_057637.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP62	ENST00000352066.8	c.1518C>T	p.Cys506Cys	synonymous_variant	3/3	1	NM_016553.5	ENSP00000305503.3

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 550 AN: 152128 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00485

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00300 AC: 752 AN: 250340 Hom.: 0 AF XY: 0.00304 AC XY: 412 AN XY: 135464

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00186

Gnomad FIN exome AF: 0.00241

Gnomad NFE exome AF: 0.00486

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00426 AC: 6233 AN: 1461636 Hom.: 14 Cov.: 31 AF XY: 0.00421 AC XY: 3063 AN XY: 727144

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.00271

Gnomad4 NFE exome AF: 0.00504

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00361 AC: 550 AN: 152246 Hom.: 8 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74438

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00485

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00412 Hom.: 2

Bravo AF: 0.00348

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00409

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.8
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs144664411; hg19: chr19-50411547;