chr5-174204791-T-C

Variant names:

• chr5-174204791-T-C
• rs17076993
• ENST00000521585.5:c.214-409T>C

Variant summary

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

The ENST00000521585.5(NSG2):​c.214-409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,262 control chromosomes in the GnomAD database, including 1,901 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 0.11 (1901 hom., cov: 32)
• Consequence: NSG2 ENST00000521585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 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.214-409T>C		intron_variant	Intron 3 of 4	4		ENSP00000429863.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16489 AN: 152144 Hom.: 1901 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.108 AC: 16491 AN: 152262 Hom.: 1901 Cov.: 32 AF XY: 0.115 AC XY: 8560 AN XY: 74448

African (AFR) AF: 0.0238 AC: 988 AN: 41560

American (AMR) AF: 0.241 AC: 3691 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2824 AN: 5164

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4816

European-Finnish (FIN) AF: 0.0756 AC: 802 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6325 AN: 68022

Other (OTH) AF: 0.106 AC: 225 AN: 2114

Alfa AF: 0.0826 Hom.: 268

Bravo AF: 0.118

Asia WGS AF: 0.398 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-1.4
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: rs17076993; hg19: chr5-173631794;