2-233005656-G-C

Variant names:

• chr2-233005656-G-C
• rs1104953
• NM_019850.3:c.-75+7412C>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+7412C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,960 control chromosomes in the GnomAD database, including 11,877 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 0.38 (11877 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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 (EAS) allele frequency at 95% confidence interval = 0.834 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+7412C>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+7412C>G		intron	N/A	ENSP00000264051.3
	ENSG00000222001	ENST00000783807.1		n.68-7099G>C		intron	N/A
	ENSG00000222001	ENST00000783808.1		n.28-7099G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57401 AN: 151842 Hom.: 11862 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.378 AC: 57451 AN: 151960 Hom.: 11877 Cov.: 32 AF XY: 0.386 AC XY: 28638 AN XY: 74266

African (AFR) AF: 0.357 AC: 14765 AN: 41410

American (AMR) AF: 0.424 AC: 6473 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4410 AN: 5160

South Asian (SAS) AF: 0.550 AC: 2641 AN: 4804

European-Finnish (FIN) AF: 0.335 AC: 3543 AN: 10566

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23084 AN: 67964

Other (OTH) AF: 0.393 AC: 831 AN: 2114

Alfa AF: 0.347 Hom.: 1227

Bravo AF: 0.386

Asia WGS AF: 0.684 AC: 2376 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	3.6
DANN	Benign	0.53
PhyloP100		1.2
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: rs1104953; hg19: chr2-233870366;