5-174220709-C-T

Variant names:

• chr5-174220709-C-T
• rs4295404
• ENST00000521585.5:c.*18+15405C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521585.5(NSG2):​c.*18+15405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,098 control chromosomes in the GnomAD database, including 6,545 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 0.29 (6545 hom., cov: 32)
• Consequence: NSG2 ENST00000521585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 2 publications found

Genes affected

NSG2 (HGNC:24955): (neuronal vesicle trafficking associated 2) Predicted to enable clathrin light chain binding activity. Predicted to be involved in clathrin coat assembly and endosomal transport. Located in Golgi apparatus. [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 = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSG2	ENST00000521585.5	c.*18+15405C>T		intron_variant	Intron 4 of 4	4		ENSP00000429863.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43632 AN: 151980 Hom.: 6539 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43654 AN: 152098 Hom.: 6545 Cov.: 32 AF XY: 0.287 AC XY: 21341 AN XY: 74330

African (AFR) AF: 0.218 AC: 9059 AN: 41494

American (AMR) AF: 0.341 AC: 5215 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2598 AN: 5166

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2764 AN: 10578

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20900 AN: 67980

Other (OTH) AF: 0.292 AC: 616 AN: 2110

Alfa AF: 0.304 Hom.: 12096

Bravo AF: 0.294

Asia WGS AF: 0.374 AC: 1297 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	0.92
DANN	Benign	0.60
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4295404; hg19: chr5-173647712;