rs10933423

Variant names:

• chr2-233006757-A-C
• rs10933423
• NM_019850.3:c.-75+6311T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019850.3(NGEF):​c.-75+6311T>G 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 152,052 control chromosomes in the GnomAD database, including 6,711 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 (6711 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 5 publications found

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]

ENSG00000222001 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-75+6311T>G		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+6042T>G		intron_variant	Intron 1 of 14		XP_011509225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.-75+6311T>G		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3
ENSG00000222001	ENST00000783807.1	n.68-5998A>C		intron_variant	Intron 1 of 3
ENSG00000222001	ENST00000783808.1	n.28-5998A>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38235 AN: 151934 Hom.: 6697 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.252 AC: 38296 AN: 152052 Hom.: 6711 Cov.: 32 AF XY: 0.245 AC XY: 18207 AN XY: 74336

African (AFR) AF: 0.495 AC: 20496 AN: 41426

American (AMR) AF: 0.189 AC: 2893 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3470

East Asian (EAS) AF: 0.0748 AC: 388 AN: 5186

South Asian (SAS) AF: 0.146 AC: 705 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1747 AN: 10566

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11155 AN: 68002

Other (OTH) AF: 0.203 AC: 428 AN: 2104

Alfa AF: 0.182 Hom.: 5191

Bravo AF: 0.267

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.99
DANN	Benign	0.61
PhyloP100		0.56
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

Other links and lift over

dbSNP: rs10933423; hg19: chr2-233871467;