5-174192941-C-T

Variant names:

• chr5-174192941-C-T
• rs17076974
• ENST00000521585.5:c.214-12259C>T

Variant summary

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

The ENST00000521585.5(NSG2):​c.214-12259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,928 control chromosomes in the GnomAD database, including 14,537 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 0.43 (14537 hom., cov: 32)
• Consequence: NSG2 ENST00000521585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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.214-12259C>T		intron_variant	Intron 3 of 4	4		ENSP00000429863.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65766 AN: 151810 Hom.: 14533 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.433 AC: 65787 AN: 151928 Hom.: 14537 Cov.: 32 AF XY: 0.423 AC XY: 31411 AN XY: 74260

African (AFR) AF: 0.408 AC: 16902 AN: 41408

American (AMR) AF: 0.373 AC: 5703 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1249 AN: 5150

South Asian (SAS) AF: 0.360 AC: 1732 AN: 4806

European-Finnish (FIN) AF: 0.384 AC: 4061 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32852 AN: 67944

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.453 Hom.: 6650

Bravo AF: 0.431

Asia WGS AF: 0.331 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.45
PhyloP100		-0.53
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: rs17076974; hg19: chr5-173619944;