chr2-233009689-T-C

Variant names:

• chr2-233009689-T-C
• rs13383577
• NM_019850.3:c.-75+3379A>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+3379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,310 control chromosomes in the GnomAD database, including 15,855 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 0.44 (15855 hom., cov: 30)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 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+3379A>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+3379A>G		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.68-3066T>C		intron	N/A
	ENSG00000222001	ENST00000783808.1		n.28-3066T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67082 AN: 151226 Hom.: 15845 Cov.: 30

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.444 AC: 67117 AN: 151310 Hom.: 15855 Cov.: 30 AF XY: 0.435 AC XY: 32093 AN XY: 73798

African (AFR) AF: 0.382 AC: 15749 AN: 41218

American (AMR) AF: 0.416 AC: 6325 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3466

East Asian (EAS) AF: 0.0659 AC: 339 AN: 5148

South Asian (SAS) AF: 0.282 AC: 1351 AN: 4786

European-Finnish (FIN) AF: 0.513 AC: 5295 AN: 10316

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34747 AN: 67858

Other (OTH) AF: 0.445 AC: 934 AN: 2098

Alfa AF: 0.494 Hom.: 30594

Bravo AF: 0.429

Asia WGS AF: 0.180 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.49
PhyloP100		-0.28
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: rs13383577; hg19: chr2-233874399;