rs10502190

Positions:

• chr11-114557218-G-A
• chr11-114557218-G-C

Variant summary

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

The NM_001395504.1(NXPE1):​c.-211+2580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,956 control chromosomes in the GnomAD database, including 4,718 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 0.21 (4718 hom., cov: 30)
• Consequence: NXPE1 NM_001395504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

Genes affected

NXPE1 (HGNC:28527): (neurexophilin and PC-esterase domain family member 1) Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NXPE2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPE1	NM_001395504.1	c.-211+2580C>T		intron_variant		ENST00000534921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPE1	ENST00000534921.3	c.-211+2580C>T		intron_variant		3	NM_001395504.1	P1
NXPE1	ENST00000251921.6	c.-357+2580C>T		intron_variant		1
NXPE1	ENST00000696071.1	c.-99+2580C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32481 AN: 151838 Hom.: 4703 Cov.: 30

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32534 AN: 151956 Hom.: 4718 Cov.: 30 AF XY: 0.212 AC XY: 15761 AN XY: 74286

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.211

Alfa AF: 0.0780 Hom.: 100

Bravo AF: 0.229

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs10502190; hg19: chr11-114427940;