rs884089

Variant names:

• chr2-233001319-C-G
• rs884089
• NM_019850.3:c.-75+11749G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-233001319-C-G
• chr2-233001319-C-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+11749G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,144 control chromosomes in the GnomAD database, including 11,255 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 0.37 (11255 hom., cov: 33)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-75+11749G>C		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+11480G>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.-75+11749G>C		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3
ENSG00000222001	ENST00000783807.1	n.68-11436C>G		intron_variant	Intron 1 of 3
ENSG00000222001	ENST00000783808.1	n.27+3018C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56568 AN: 152026 Hom.: 11244 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.372 AC: 56619 AN: 152144 Hom.: 11255 Cov.: 33 AF XY: 0.372 AC XY: 27672 AN XY: 74362

African (AFR) AF: 0.482 AC: 20024 AN: 41514

American (AMR) AF: 0.367 AC: 5614 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3274 AN: 5162

South Asian (SAS) AF: 0.354 AC: 1707 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3237 AN: 10568

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20456 AN: 67992

Other (OTH) AF: 0.356 AC: 754 AN: 2116

Alfa AF: 0.327 Hom.: 1054

Bravo AF: 0.387

Asia WGS AF: 0.494 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		-0.57
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: rs884089; hg19: chr2-233866029;