rs938572

Variant names:

• chr2-232976590-G-A
• rs938572
• NM_019850.3:c.-74-1626C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-232976590-G-A
• chr2-232976590-G-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.-74-1626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,106 control chromosomes in the GnomAD database, including 22,805 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 0.54 (22805 hom., cov: 33)
• Consequence: NGEF NM_019850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGEF	NM_019850.3	c.-74-1626C>T		intron_variant	Intron 1 of 14	ENST00000264051.8	NP_062824.2
NGEF	XM_011510923.4	c.-74-1626C>T		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.-74-1626C>T		intron_variant	Intron 1 of 14	1	NM_019850.3	ENSP00000264051.3
ENSG00000222001	ENST00000783807.1	n.68-36165G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82004 AN: 151988 Hom.: 22784 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.540 AC: 82068 AN: 152106 Hom.: 22805 Cov.: 33 AF XY: 0.533 AC XY: 39651 AN XY: 74360

African (AFR) AF: 0.581 AC: 24100 AN: 41506

American (AMR) AF: 0.513 AC: 7844 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3472

East Asian (EAS) AF: 0.137 AC: 710 AN: 5170

South Asian (SAS) AF: 0.385 AC: 1855 AN: 4816

European-Finnish (FIN) AF: 0.575 AC: 6090 AN: 10584

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38418 AN: 67946

Other (OTH) AF: 0.499 AC: 1055 AN: 2114

Alfa AF: 0.544 Hom.: 3840

Bravo AF: 0.536

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		0.055
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: rs938572; hg19: chr2-233841300;