rs3743500

chr15-73633441-A-Cchr15-73633441-A-Gchr15-73633441-A-T

Variant summary

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

The ENST00000351217.10(NPTN):c.-226T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 397,134 control chromosomes in the GnomAD database, including 51,528 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 0.49 (18531 hom., cov: 32)
  • Exomes 𝑓: 0.52 (32997 hom.)
• Consequence: NPTN ENST00000351217.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

Genes affected

NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 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
NPTN	ENST00000351217.10	c.-226T>G		5_prime_UTR_variant	1/8	1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74446 AN: 151802 Hom.: 18518 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.516 AC: 126459 AN: 245214 Hom.: 32997 Cov.: 3 AF XY: 0.514 AC XY: 65006 AN XY: 126554

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.529

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.490 AC: 74515 AN: 151920 Hom.: 18531 Cov.: 32 AF XY: 0.492 AC XY: 36534 AN XY: 74244

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.480

Alfa AF: 0.353 Hom.: 912

Bravo AF: 0.489

Asia WGS AF: 0.465 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743500; hg19: chr15-73925782; COSMIC: COSV54740320; COSMIC: COSV54740320;