2-233012355-T-C

Variant names:

• chr2-233012355-T-C
• rs6725244
• NM_019850.3:c.-75+713A>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+713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,460 control chromosomes in the GnomAD database, including 14,768 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 0.43 (14768 hom., cov: 32)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-75+713A>G		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-75+444A>G		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+713A>G		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 64707 AN: 150348 Hom.: 14765 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.0393

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.430 AC: 64727 AN: 150460 Hom.: 14768 Cov.: 32 AF XY: 0.424 AC XY: 31207 AN XY: 73526

African (AFR) AF: 0.376 AC: 15030 AN: 39972

American (AMR) AF: 0.365 AC: 5557 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3468

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5174

South Asian (SAS) AF: 0.280 AC: 1350 AN: 4824

European-Finnish (FIN) AF: 0.529 AC: 5590 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33604 AN: 67976

Other (OTH) AF: 0.434 AC: 904 AN: 2082

Alfa AF: 0.465 Hom.: 70762

Bravo AF: 0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs6725244; hg19: chr2-233877065; COSMIC: COSV50917227; COSMIC: COSV50917227;