4-4363339-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513555.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSG1	ENST00000513555.5	TSL:1	c.-952+14868C>T		intron	N/A	ENSP00000426358.1	P42857-1
	NSG1	ENST00000421177.6	TSL:5	c.-1660+14868C>T		intron	N/A	ENSP00000388823.2	P42857-1

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

African (AFR) AF: 0.300 AC: 12456 AN: 41504

American (AMR) AF: 0.485 AC: 7419 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2088 AN: 3472

East Asian (EAS) AF: 0.373 AC: 1923 AN: 5162

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4820

European-Finnish (FIN) AF: 0.534 AC: 5653 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35859 AN: 67978

Other (OTH) AF: 0.464 AC: 981 AN: 2114

Alfa AF: 0.505 Hom.: 72899

Bravo AF: 0.442

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.80
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4689340; hg19: chr4-4365066;