rs954526

Variant names:

• chr2-232975353-A-G
• rs954526
• NM_019850.3:c.-74-389T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019850.3(NGEF):​c.-74-389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,062 control chromosomes in the GnomAD database, including 29,667 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 0.61 (29667 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-74-389T>C		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-74-389T>C		intron_variant	Intron 1 of 14		XP_011509225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.-74-389T>C		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3
ENSG00000222001	ENST00000783807.1	n.68-37402A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92260 AN: 151944 Hom.: 29617 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.607 AC: 92356 AN: 152062 Hom.: 29667 Cov.: 32 AF XY: 0.599 AC XY: 44520 AN XY: 74354

African (AFR) AF: 0.795 AC: 32972 AN: 41484

American (AMR) AF: 0.506 AC: 7730 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3472

East Asian (EAS) AF: 0.155 AC: 805 AN: 5180

South Asian (SAS) AF: 0.391 AC: 1882 AN: 4814

European-Finnish (FIN) AF: 0.603 AC: 6377 AN: 10580

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39380 AN: 67942

Other (OTH) AF: 0.547 AC: 1152 AN: 2106

Alfa AF: 0.597 Hom.: 3471

Bravo AF: 0.607

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		0.24
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: rs954526; hg19: chr2-233840063;