rs216392

Variant names:

• chr5-37292137-G-A
• rs216392
• NM_153485.3:c.4038-99C>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.4038-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,116,492 control chromosomes in the GnomAD database, including 34,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (13827 hom., cov: 33)
  • Exomes 𝑓: 0.18 (20890 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.138
• Publications: 4 publications found

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]

NUP155 Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atrial fibrillation, familial, 15

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 5-37292137-G-A is Benign according to our data. Variant chr5-37292137-G-A is described in ClinVar as Benign. ClinVar VariationId is 1290619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153485.3. 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
	NUP155	NM_153485.3	MANE Select	c.4038-99C>T		intron	N/A	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3861-99C>T		intron	N/A	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3846-99C>T		intron	N/A	NP_001265241.1	E9PF10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP155	ENST00000231498.8	TSL:1 MANE Select	c.4038-99C>T		intron	N/A	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3861-99C>T		intron	N/A	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3846-99C>T		intron	N/A	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51033 AN: 151964 Hom.: 13778 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.182 AC: 175092 AN: 964414 Hom.: 20890 AF XY: 0.181 AC XY: 90283 AN XY: 499408

African (AFR) AF: 0.770 AC: 17865 AN: 23196

American (AMR) AF: 0.230 AC: 9316 AN: 40496

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4114 AN: 22610

East Asian (EAS) AF: 0.0981 AC: 3495 AN: 35630

South Asian (SAS) AF: 0.208 AC: 15280 AN: 73330

European-Finnish (FIN) AF: 0.201 AC: 10399 AN: 51800

Middle Eastern (MID) AF: 0.197 AC: 946 AN: 4812

European-Non Finnish (NFE) AF: 0.157 AC: 104810 AN: 668892

Other (OTH) AF: 0.203 AC: 8867 AN: 43648

GnomAD4 genome AF: 0.336 AC: 51148 AN: 152078 Hom.: 13827 Cov.: 33 AF XY: 0.335 AC XY: 24893 AN XY: 74350

African (AFR) AF: 0.755 AC: 31300 AN: 41464

American (AMR) AF: 0.247 AC: 3772 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.125 AC: 648 AN: 5176

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4810

European-Finnish (FIN) AF: 0.200 AC: 2117 AN: 10564

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10886 AN: 67996

Other (OTH) AF: 0.311 AC: 656 AN: 2112

Alfa AF: 0.272 Hom.: 1539

Bravo AF: 0.356

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.26
PhyloP100		0.14
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: rs216392; hg19: chr5-37292239; COSMIC: COSV51533712;