rs4973062

Positions:

• chr2-232993926-C-T

Variant summary

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

The NM_019850.3(NGEF):​c.-74-18962G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,862 control chromosomes in the GnomAD database, including 31,762 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 0.64 (31762 hom., cov: 30)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-74-18962G>A		intron_variant		ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+18873G>A		intron_variant			XP_011509225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.-74-18962G>A		intron_variant		1	NM_019850.3	ENSP00000264051.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96869 AN: 151744 Hom.: 31723 Cov.: 30

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.638 AC: 96959 AN: 151862 Hom.: 31762 Cov.: 30 AF XY: 0.640 AC XY: 47537 AN XY: 74220

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.624

Alfa AF: 0.587 Hom.: 53819

Bravo AF: 0.651

Asia WGS AF: 0.838 AC: 2912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.88

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: rs4973062; hg19: chr2-233858636;