14-23476157-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042635.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGDN	NM_001042635.2	MANE Select	c.544+5A>G		splice_region intron	N/A	NP_001036100.1
	NGDN	NM_015514.2		c.544+5A>G		splice_region intron	N/A	NP_056329.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGDN	ENST00000408901.8	TSL:1 MANE Select	c.544+5A>G		splice_region intron	N/A	ENSP00000386134.3
	NGDN	ENST00000397154.7	TSL:1	c.544+5A>G		splice_region intron	N/A	ENSP00000380340.3
	NGDN	ENST00000703193.1		n.1148A>G		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes AF: 0.768 AC: 192961 AN: 251362 AF XY: 0.774

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 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

African (AFR) AF: 0.642 AC: 21500 AN: 33478

American (AMR) AF: 0.690 AC: 30852 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 18702 AN: 26136

East Asian (EAS) AF: 0.676 AC: 26852 AN: 39698

South Asian (SAS) AF: 0.750 AC: 64690 AN: 86256

European-Finnish (FIN) AF: 0.829 AC: 44271 AN: 53416

Middle Eastern (MID) AF: 0.801 AC: 4622 AN: 5768

European-Non Finnish (NFE) AF: 0.830 AC: 922946 AN: 1111878

Other (OTH) AF: 0.790 AC: 47716 AN: 60392

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

African (AFR) AF: 0.643 AC: 26645 AN: 41452

American (AMR) AF: 0.725 AC: 11069 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2493 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3338 AN: 5164

South Asian (SAS) AF: 0.741 AC: 3575 AN: 4824

European-Finnish (FIN) AF: 0.824 AC: 8724 AN: 10590

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.828 AC: 56323 AN: 68006

Other (OTH) AF: 0.763 AC: 1606 AN: 2106

Alfa AF: 0.794 Hom.: 22849

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		0.076
Mutation Taster		=80/20	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295706; hg19: chr14-23945366; COSMIC: COSV68142876; COSMIC: COSV68142876;