19-49928131-G-A

Variant names:

• chr19-49928131-G-A
• rs3826777
• NM_016553.5:c.-199-316C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000269179 (HGNC:):

ATF5 (HGNC:790): (activating transcription factor 5) Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of cell cycle process; and regulation of transcription, DNA-templated. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016553.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP62	NM_016553.5	MANE Select	c.-199-316C>T		intron	N/A	NP_057637.2
	IL4I1	NM_001258017.2		c.-349-316C>T		intron	N/A	NP_001244946.1	Q96RQ9-2
	IL4I1	NM_001258018.2		c.-407-316C>T		intron	N/A	NP_001244947.1	Q96RQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP62	ENST00000352066.8	TSL:1 MANE Select	c.-199-316C>T		intron	N/A	ENSP00000305503.3	P37198
	IL4I1	ENST00000341114.7	TSL:1	c.-349-316C>T		intron	N/A	ENSP00000342557.2	Q96RQ9-2
	IL4I1	ENST00000595948.5	TSL:1	c.-407-316C>T		intron	N/A	ENSP00000472474.1	Q96RQ9-2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 4 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.289 AC: 11 AN: 38

Other (OTH) AF: 0.250 AC: 4 AN: 16

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

African (AFR) AF: 0.246 AC: 10206 AN: 41480

American (AMR) AF: 0.418 AC: 6392 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3472

East Asian (EAS) AF: 0.430 AC: 2216 AN: 5156

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4824

European-Finnish (FIN) AF: 0.442 AC: 4676 AN: 10576

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24906 AN: 67958

Other (OTH) AF: 0.348 AC: 735 AN: 2110

Alfa AF: 0.356 Hom.: 6830

Bravo AF: 0.336

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		-0.20
Mutation Taster		=299/1	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: rs3826777; hg19: chr19-50431388; COSMIC: COSV61311459; COSMIC: COSV61311459;