rs13404304

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019850.3(NGEF):​c.-75+13281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,188 control chromosomes in the GnomAD database, including 5,109 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 0.25 ( 5109 hom., cov: 33)

Consequence

NGEF
NM_019850.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131
Variant links:
Genes affected
NGEF (HGNC:7807): (neuronal guanine nucleotide exchange factor) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including activation of GTPase activity; ephrin receptor signaling pathway; and negative regulation of dendritic spine morphogenesis. Predicted to be located in cytosol. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NGEFNM_019850.3 linkuse as main transcriptc.-75+13281C>T intron_variant ENST00000264051.8
NGEFXM_011510923.4 linkuse as main transcriptc.-75+13012C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NGEFENST00000264051.8 linkuse as main transcriptc.-75+13281C>T intron_variant 1 NM_019850.3 Q8N5V2-1

Frequencies

GnomAD3 genomes
AF:
0.252
AC:
38349
AN:
152070
Hom.:
5100
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.257
Gnomad AMI
AF:
0.194
Gnomad AMR
AF:
0.236
Gnomad ASJ
AF:
0.191
Gnomad EAS
AF:
0.0470
Gnomad SAS
AF:
0.0744
Gnomad FIN
AF:
0.275
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.283
Gnomad OTH
AF:
0.235
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.252
AC:
38377
AN:
152188
Hom.:
5109
Cov.:
33
AF XY:
0.246
AC XY:
18267
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.257
Gnomad4 AMR
AF:
0.236
Gnomad4 ASJ
AF:
0.191
Gnomad4 EAS
AF:
0.0469
Gnomad4 SAS
AF:
0.0743
Gnomad4 FIN
AF:
0.275
Gnomad4 NFE
AF:
0.283
Gnomad4 OTH
AF:
0.231
Alfa
AF:
0.270
Hom.:
5467
Bravo
AF:
0.248
Asia WGS
AF:
0.0770
AC:
270
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.24
DANN
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13404304; hg19: chr2-233864497; API