4-4363339-C-T

Position:

• chr4-4363339-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513555.5(NSG1):​c.-952+14868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,136 control chromosomes in the GnomAD database, including 16,788 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 0.46 (16788 hom., cov: 34)
• Consequence: NSG1 ENST00000513555.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

Genes affected

NSG1 (HGNC:18790): (neuronal vesicle trafficking associated 1) Predicted to enable clathrin light chain binding activity. Involved in apoptotic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSG1	ENST00000513555.5	c.-952+14868C>T		intron_variant		1		ENSP00000426358.1
NSG1	ENST00000421177.6	c.-1660+14868C>T		intron_variant		5		ENSP00000388823.2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69530 AN: 152018 Hom.: 16763 Cov.: 34

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.457 AC: 69593 AN: 152136 Hom.: 16788 Cov.: 34 AF XY: 0.460 AC XY: 34193 AN XY: 74384

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.464

Alfa AF: 0.515 Hom.: 32126

Bravo AF: 0.442

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.80

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: rs4689340; hg19: chr4-4365066;