15-73633441-A-C

Variant names:

• chr15-73633441-A-C
• rs3743500
• ENST00000351217.10:c.-226T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPTN	NM_012428.4	c.-226T>G		upstream_gene_variant		ENST00000345330.9	NP_036560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTN	ENST00000345330.9	c.-226T>G		upstream_gene_variant		1	NM_012428.4	ENSP00000290401.4

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

African (AFR) AF: 0.424 AC: 2823 AN: 6662

American (AMR) AF: 0.529 AC: 3607 AN: 6824

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 3998 AN: 8842

East Asian (EAS) AF: 0.595 AC: 12874 AN: 21646

South Asian (SAS) AF: 0.432 AC: 3745 AN: 8662

European-Finnish (FIN) AF: 0.535 AC: 11008 AN: 20578

Middle Eastern (MID) AF: 0.476 AC: 579 AN: 1216

European-Non Finnish (NFE) AF: 0.516 AC: 79930 AN: 155020

Other (OTH) AF: 0.501 AC: 7895 AN: 15764

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

African (AFR) AF: 0.422 AC: 17506 AN: 41462

American (AMR) AF: 0.528 AC: 8066 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2708 AN: 5092

South Asian (SAS) AF: 0.446 AC: 2147 AN: 4816

European-Finnish (FIN) AF: 0.528 AC: 5591 AN: 10580

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35231 AN: 67908

Other (OTH) AF: 0.480 AC: 1012 AN: 2108

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
PhyloP100		-0.50
PromoterAI		-0.022	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

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