rs4466877

Variant names:

• chr11-114516380-G-A
• rs4466877
• XM_017017207.2:c.-639-1176G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017017207.2(NXPE2):​c.-639-1176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,986 control chromosomes in the GnomAD database, including 5,473 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 0.23 (5473 hom., cov: 31)
• Consequence: NXPE2 XM_017017207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 5 publications found

Genes affected

NXPE2 (HGNC:26331): (neurexophilin and PC-esterase domain family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPE2	XM_017017207.2	c.-639-1176G>A		intron_variant	Intron 1 of 11		XP_016872696.1
NXPE2	XM_017017209.2	c.-482-10243G>A		intron_variant	Intron 1 of 10		XP_016872698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34402 AN: 151868 Hom.: 5463 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.227 AC: 34458 AN: 151986 Hom.: 5473 Cov.: 31 AF XY: 0.224 AC XY: 16634 AN XY: 74288

African (AFR) AF: 0.443 AC: 18324 AN: 41398

American (AMR) AF: 0.220 AC: 3364 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4812

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10564

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9081 AN: 67984

Other (OTH) AF: 0.219 AC: 460 AN: 2102

Alfa AF: 0.240 Hom.: 3447

Bravo AF: 0.243

Asia WGS AF: 0.129 AC: 451 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	6.0
DANN	Benign	0.61
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs4466877; hg19: chr11-114387102;