rs3811588

Variant names:

• chr2-233011265-G-A
• rs3811588
• NM_019850.3:c.-75+1803C>T

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+1803C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,818 control chromosomes in the GnomAD database, including 1,187 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 0.12 (1187 hom., cov: 31)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 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+1803C>T		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+1803C>T		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.68-1490G>A		intron	N/A
	ENSG00000222001	ENST00000783808.1		n.28-1490G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17738 AN: 151698 Hom.: 1179 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0739

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.117 AC: 17764 AN: 151818 Hom.: 1187 Cov.: 31 AF XY: 0.118 AC XY: 8789 AN XY: 74194

African (AFR) AF: 0.130 AC: 5360 AN: 41360

American (AMR) AF: 0.124 AC: 1896 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 256 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1077 AN: 5134

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4812

European-Finnish (FIN) AF: 0.0837 AC: 885 AN: 10574

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

European-Non Finnish (NFE) AF: 0.100 AC: 6817 AN: 67898

Other (OTH) AF: 0.121 AC: 255 AN: 2106

Alfa AF: 0.107 Hom.: 1585

Bravo AF: 0.117

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.66
PhyloP100		-0.25
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: rs3811588; hg19: chr2-233875975;