rs217776

Variant names:

• chr5-37350288-C-A
• rs217776
• NM_153485.3:c.724-23G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37350288-C-A
• chr5-37350288-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153485.3(NUP155):​c.724-23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,524,262 control chromosomes in the GnomAD database, including 39,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (12380 hom., cov: 32)
  • Exomes 𝑓: 0.18 (27036 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.315

Genes affected

NUP155 (HGNC:8063): (nucleoporin 155) Nucleoporins are proteins that play an important role in the assembly and functioning of the nuclear pore complex (NPC) which regulates the movement of macromolecules across the nuclear envelope (NE). The protein encoded by this gene plays a role in the fusion of NE vesicles and formation of the double membrane NE. The protein may also be involved in cardiac physiology and may be associated with the pathogenesis of atrial fibrillation. Alternative splicing results in multiple transcript variants of this gene. A pseudogene associated with this gene is located on chromosome 6. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-37350288-C-A is Benign according to our data. Variant chr5-37350288-C-A is described in ClinVar as [Benign]. Clinvar id is 1180263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.724-23G>T		intron_variant	Intron 6 of 34	ENST00000231498.8	NP_705618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498.8	c.724-23G>T		intron_variant	Intron 6 of 34	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.547-23G>T		intron_variant	Intron 6 of 34	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.724-23G>T		intron_variant	Intron 6 of 33	1		ENSP00000422019.1
NUP155	ENST00000507233.1	n.-86G>T		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48985 AN: 151860 Hom.: 12343 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.215 AC: 53837 AN: 250426 AF XY: 0.204

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.176 AC: 241335 AN: 1372284 Hom.: 27036 Cov.: 22 AF XY: 0.176 AC XY: 120756 AN XY: 687612

Gnomad4 AFR exome AF: 0.725 AC: 23068 AN: 31806

Gnomad4 AMR exome AF: 0.227 AC: 10090 AN: 44486

Gnomad4 ASJ exome AF: 0.183 AC: 4667 AN: 25544

Gnomad4 EAS exome AF: 0.0982 AC: 3849 AN: 39180

Gnomad4 SAS exome AF: 0.208 AC: 17475 AN: 84172

Gnomad4 FIN exome AF: 0.201 AC: 10708 AN: 53254

Gnomad4 NFE exome AF: 0.154 AC: 159132 AN: 1030858

Gnomad4 Remaining exome AF: 0.196 AC: 11269 AN: 57394

GnomAD4 genome AF: 0.323 AC: 49084 AN: 151978 Hom.: 12380 Cov.: 32 AF XY: 0.321 AC XY: 23866 AN XY: 74286

Gnomad4 AFR AF: 0.709 AC: 0.709393 AN: 0.709393

Gnomad4 AMR AF: 0.242 AC: 0.242001 AN: 0.242001

Gnomad4 ASJ AF: 0.180 AC: 0.180115 AN: 0.180115

Gnomad4 EAS AF: 0.124 AC: 0.123646 AN: 0.123646

Gnomad4 SAS AF: 0.209 AC: 0.209215 AN: 0.209215

Gnomad4 FIN AF: 0.201 AC: 0.200645 AN: 0.200645

Gnomad4 NFE AF: 0.160 AC: 0.159613 AN: 0.159613

Gnomad4 OTH AF: 0.299 AC: 0.298861 AN: 0.298861

Alfa AF: 0.167 Hom.: 1450

Bravo AF: 0.340

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.63
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)		0.010		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: rs217776; hg19: chr5-37350390; COSMIC: COSV51528201; COSMIC: COSV51528201;