rs1104953

chr2-233005656-G-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+7412C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,960 control chromosomes in the GnomAD database, including 11,877 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 0.38 (11877 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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 (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGEF	NM_019850.3	c.-75+7412C>G		intron_variant		ENST00000264051.8
NGEF	XM_011510923.4	c.-75+7143C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGEF	ENST00000264051.8	c.-75+7412C>G		intron_variant		1	NM_019850.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57401 AN: 151842 Hom.: 11862 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.378 AC: 57451 AN: 151960 Hom.: 11877 Cov.: 32 AF XY: 0.386 AC XY: 28638 AN XY: 74266

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.393

Alfa AF: 0.347 Hom.: 1227

Bravo AF: 0.386

Asia WGS AF: 0.684 AC: 2376 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	3.6
Dann	Benign	0.53

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: rs1104953; hg19: chr2-233870366;