14-23476157-A-G

Variant names:

• chr14-23476157-A-G
• rs2295706
• NM_001042635.2:c.544+5A>G

Variant summary

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

The NM_001042635.2(NGDN):​c.544+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,613,832 control chromosomes in the GnomAD database, including 523,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (43781 hom., cov: 32)
  • Exomes 𝑓: 0.81 (480118 hom.)
• Consequence: NGDN NM_001042635.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005421
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGDN	NM_001042635.2	c.544+5A>G		splice_region_variant, intron_variant	Intron 7 of 10	ENST00000408901.8	NP_001036100.1
NGDN	NM_015514.2	c.544+5A>G		splice_region_variant, intron_variant	Intron 7 of 9		NP_056329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGDN	ENST00000408901.8	c.544+5A>G		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_001042635.2	ENSP00000386134.3

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114637 AN: 151972 Hom.: 43782 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.769

GnomAD3 exomes AF: 0.768 AC: 192961 AN: 251362 Hom.: 74850 AF XY: 0.774 AC XY: 105122 AN XY: 135848

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.709

Gnomad EAS exome AF: 0.645

Gnomad SAS exome AF: 0.748

Gnomad FIN exome AF: 0.828

Gnomad NFE exome AF: 0.829

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.809 AC: 1182151 AN: 1461742 Hom.: 480118 Cov.: 52 AF XY: 0.808 AC XY: 587751 AN XY: 727180

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.754 AC: 114673 AN: 152090 Hom.: 43781 Cov.: 32 AF XY: 0.754 AC XY: 56087 AN XY: 74366

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.763

Alfa AF: 0.795 Hom.: 22677

Bravo AF: 0.741

Asia WGS AF: 0.684 AC: 2381 AN: 3478

EpiCase AF: 0.817

EpiControl AF: 0.816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000054
dbscSNV1_RF	Benign	0.036
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: rs2295706; hg19: chr14-23945366; COSMIC: COSV68142876; COSMIC: COSV68142876;