rs3840846

Positions:

• chr15-73633677-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000351217.10(NPTN):​c.-463del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 156,178 control chromosomes in the GnomAD database, including 28 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (27 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: NPTN ENST00000351217.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0146 (2229/152352) while in subpopulation EAS AF= 0.0542 (281/5184). AF 95% confidence interval is 0.049. There are 27 homozygotes in gnomad4. There are 1107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2229 AD gene.

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.-463del		5_prime_UTR_variant	1/8	1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2228 AN: 152234 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00357

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0136 AC: 52 AN: 3826 Hom.: 1 Cov.: 0 AF XY: 0.0124 AC XY: 27 AN XY: 2174

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00769

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.00478

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0146 AC: 2229 AN: 152352 Hom.: 27 Cov.: 32 AF XY: 0.0149 AC XY: 1107 AN XY: 74506

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00357

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.0152

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3840846; hg19: chr15-73926018;