4-4352929-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 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+4458T>G		intron	N/A	ENSP00000426358.1	P42857-1
	NSG1	ENST00000421177.6	TSL:5	c.-1660+4458T>G		intron	N/A	ENSP00000388823.2	P42857-1

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

African (AFR) AF: 0.390 AC: 16190 AN: 41462

American (AMR) AF: 0.169 AC: 2584 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5164

South Asian (SAS) AF: 0.156 AC: 753 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2616 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8461 AN: 68002

Other (OTH) AF: 0.194 AC: 410 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.22
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7692312;

hg19: chr4-4354656;