4-4352929-T-G

Variant names:

• chr4-4352929-T-G
• rs7692312
• ENST00000513555.5:c.-952+4458T>G

Variant summary

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

The ENST00000513555.5(NSG1):​c.-952+4458T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,106 control chromosomes in the GnomAD database, including 4,730 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 0.22 (4730 hom., cov: 33)
• Consequence: NSG1 ENST00000513555.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 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+4458T>G		intron_variant	Intron 1 of 7	1		ENSP00000426358.1
NSG1	ENST00000421177.6	c.-1660+4458T>G		intron_variant	Intron 1 of 8	5		ENSP00000388823.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33192 AN: 151988 Hom.: 4728 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.218 AC: 33211 AN: 152106 Hom.: 4730 Cov.: 33 AF XY: 0.221 AC XY: 16425 AN XY: 74354

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.194

Alfa AF: 0.0738 Hom.: 88

Bravo AF: 0.221

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7692312; hg19: chr4-4354656;