rs10933424

Positions:

• chr2-233007698-T-C

Variant summary

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

The NM_019850.3(NGEF):​c.-75+5370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,254 control chromosomes in the GnomAD database, including 821 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 0.10 (821 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGEF	NM_019850.3	c.-75+5370A>G		intron_variant		ENST00000264051.8
NGEF	XM_011510923.4	c.-75+5101A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGEF	ENST00000264051.8	c.-75+5370A>G		intron_variant		1	NM_019850.3

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15199 AN: 152136 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0999 AC: 15204 AN: 152254 Hom.: 821 Cov.: 32 AF XY: 0.0998 AC XY: 7434 AN XY: 74458

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.106 Hom.: 552

Bravo AF: 0.100

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.67

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: rs10933424; hg19: chr2-233872408;