rs223116

Positions:

• chr14-23507801-A-G
• chr14-23507801-A-T

Variant summary

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

The ENST00000703257.1(NGDN):​c.871-1539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,092 control chromosomes in the GnomAD database, including 29,798 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 0.58 (29798 hom., cov: 32)
• Consequence: NGDN ENST00000703257.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

Genes affected

NGDN (HGNC:20271): (neuroguidin) Neuroguidin is an EIF4E (MIM 133440)-binding protein that interacts with CPEB (MIM 607342) and functions as a translational regulatory protein during development of the vertebrate nervous system (Jung et al., 2006 [PubMed 16705177]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGDN	ENST00000556699.2	c.929-1539A>G		intron_variant		2		A2
NGDN	ENST00000703257.1	c.871-1539A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88265 AN: 151974 Hom.: 29807 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.580 AC: 88262 AN: 152092 Hom.: 29798 Cov.: 32 AF XY: 0.587 AC XY: 43615 AN XY: 74334

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.601

Alfa AF: 0.720 Hom.: 82094

Bravo AF: 0.551

Asia WGS AF: 0.594 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs223116; hg19: chr14-23977010;