rs13404304

Variant names:

• chr2-232999787-G-A
• rs13404304
• NM_019850.3:c.-75+13281C>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+13281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,188 control chromosomes in the GnomAD database, including 5,109 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 0.25 (5109 hom., cov: 33)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.279 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	NM_019850.3	MANE Select	c.-75+13281C>T		intron	N/A	NP_062824.2	Q8N5V2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGEF	ENST00000264051.8	TSL:1 MANE Select	c.-75+13281C>T		intron	N/A	ENSP00000264051.3	Q8N5V2-1
	NGEF	ENST00000905022.1		c.-75+13281C>T		intron	N/A	ENSP00000575081.1
	NGEF	ENST00000965357.1		c.-75+13012C>T		intron	N/A	ENSP00000635416.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38349 AN: 152070 Hom.: 5100 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.252 AC: 38377 AN: 152188 Hom.: 5109 Cov.: 33 AF XY: 0.246 AC XY: 18267 AN XY: 74404

African (AFR) AF: 0.257 AC: 10662 AN: 41532

American (AMR) AF: 0.236 AC: 3611 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3466

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5182

South Asian (SAS) AF: 0.0743 AC: 359 AN: 4834

European-Finnish (FIN) AF: 0.275 AC: 2906 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19211 AN: 67984

Other (OTH) AF: 0.231 AC: 489 AN: 2114

Alfa AF: 0.267 Hom.: 9346

Bravo AF: 0.248

Asia WGS AF: 0.0770 AC: 270 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	0.24
DANN	Benign	0.65
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: rs13404304; hg19: chr2-233864497;