NM_019850.3:c.-75+5370A>G

Variant names:

• chr2-233007698-T-C
• rs10933424
• NM_019850.3:c.-75+5370A>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+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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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.-75+5370A>G		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.-75+5370A>G		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.68-5057T>C		intron	N/A
	ENSG00000222001	ENST00000783808.1		n.28-5057T>C		intron	N/A

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

African (AFR) AF: 0.0850 AC: 3533 AN: 41558

American (AMR) AF: 0.101 AC: 1544 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3470

East Asian (EAS) AF: 0.0731 AC: 379 AN: 5182

South Asian (SAS) AF: 0.108 AC: 520 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1294 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7421 AN: 68002

Other (OTH) AF: 0.0881 AC: 186 AN: 2112

Alfa AF: 0.104 Hom.: 1983

Bravo AF: 0.100

Asia WGS AF: 0.0760 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.67
PhyloP100		-1.8
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: rs10933424; hg19: chr2-233872408;