NM_019850.3:c.-74-14567T>C

Variant names:

• chr2-232989531-A-G
• rs6745724
• NM_019850.3:c.-74-14567T>C

Variant summary

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

The NM_019850.3(NGEF):​c.-74-14567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,064 control chromosomes in the GnomAD database, including 31,819 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 (31819 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	NM_019850.3	MANE Select	c.-74-14567T>C		intron	N/A	NP_062824.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	ENST00000264051.8	TSL:1 MANE Select	c.-74-14567T>C		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.68-23224A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97009 AN: 151946 Hom.: 31781 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.639 AC: 97098 AN: 152064 Hom.: 31819 Cov.: 32 AF XY: 0.640 AC XY: 47588 AN XY: 74314

African (AFR) AF: 0.720 AC: 29882 AN: 41476

American (AMR) AF: 0.639 AC: 9775 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4796 AN: 5182

South Asian (SAS) AF: 0.810 AC: 3912 AN: 4828

European-Finnish (FIN) AF: 0.544 AC: 5745 AN: 10552

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38791 AN: 67952

Other (OTH) AF: 0.627 AC: 1321 AN: 2108

Alfa AF: 0.559 Hom.: 7531

Bravo AF: 0.651

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		0.13
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: rs6745724; hg19: chr2-233854241;