4-4363339-C-T

Variant names:

• chr4-4363339-C-T
• rs4689340
• ENST00000513555.5:c.-952+14868C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSG1	ENST00000513555.5	c.-952+14868C>T		intron_variant	Intron 1 of 7	1		ENSP00000426358.1
NSG1	ENST00000421177.6	c.-1660+14868C>T		intron_variant	Intron 1 of 8	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;