rs11678490

Variant names:

• chr2-232966240-G-A
• rs11678490
• NM_019850.3:c.383+3974C>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.383+3974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,992 control chromosomes in the GnomAD database, including 2,973 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 0.19 (2973 hom., cov: 31)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 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.383+3974C>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.383+3974C>T		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.67+39132G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29143 AN: 151874 Hom.: 2976 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.192 AC: 29154 AN: 151992 Hom.: 2973 Cov.: 31 AF XY: 0.194 AC XY: 14413 AN XY: 74276

African (AFR) AF: 0.189 AC: 7834 AN: 41468

American (AMR) AF: 0.161 AC: 2462 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1761 AN: 5156

South Asian (SAS) AF: 0.252 AC: 1214 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1780 AN: 10564

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12711 AN: 67962

Other (OTH) AF: 0.194 AC: 407 AN: 2102

Alfa AF: 0.189 Hom.: 8867

Bravo AF: 0.193

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		0.55
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: rs11678490; hg19: chr2-233830950;