2-233007339-A-G

Position:

• chr2-233007339-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019850.3(NGEF):​c.-75+5729T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,128 control chromosomes in the GnomAD database, including 29,497 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 (29497 hom., cov: 33)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-75+5729T>C		intron_variant		ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+5460T>C		intron_variant			XP_011509225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGEF	ENST00000264051.8	c.-75+5729T>C		intron_variant		1	NM_019850.3	ENSP00000264051.3

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93043 AN: 152010 Hom.: 29473 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.612 AC: 93116 AN: 152128 Hom.: 29497 Cov.: 33 AF XY: 0.602 AC XY: 44753 AN XY: 74384

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.601

Alfa AF: 0.633 Hom.: 44514

Bravo AF: 0.611

Asia WGS AF: 0.325 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs10169752; hg19: chr2-233872049;