11-114556704-T-C

Variant names:

• chr11-114556704-T-C
• rs1080074
• NM_001395504.1:c.-211+3094A>G

Variant summary

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

The NM_001395504.1(NXPE1):​c.-211+3094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,040 control chromosomes in the GnomAD database, including 1,137 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 0.11 (1137 hom., cov: 30)
• Consequence: NXPE1 NM_001395504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 5 publications found

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: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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPE1	NM_001395504.1	c.-211+3094A>G		intron_variant	Intron 1 of 8	ENST00000534921.3	NP_001382433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPE1	ENST00000534921.3	c.-211+3094A>G		intron_variant	Intron 1 of 8	3	NM_001395504.1	ENSP00000439503.2
NXPE1	ENST00000251921.6	c.-357+3094A>G		intron_variant	Intron 1 of 5	1		ENSP00000251921.2
NXPE1	ENST00000696071.1	c.-99+3094A>G		intron_variant	Intron 1 of 7			ENSP00000512373.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16780 AN: 151922 Hom.: 1137 Cov.: 30

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.110 AC: 16780 AN: 152040 Hom.: 1137 Cov.: 30 AF XY: 0.112 AC XY: 8289 AN XY: 74284

African (AFR) AF: 0.0279 AC: 1158 AN: 41544

American (AMR) AF: 0.154 AC: 2346 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3466

East Asian (EAS) AF: 0.130 AC: 667 AN: 5140

South Asian (SAS) AF: 0.0706 AC: 339 AN: 4802

European-Finnish (FIN) AF: 0.165 AC: 1739 AN: 10530

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9686 AN: 67990

Other (OTH) AF: 0.133 AC: 281 AN: 2106

Alfa AF: 0.130 Hom.: 922

Bravo AF: 0.107

Asia WGS AF: 0.119 AC: 411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.74
PhyloP100		0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1080074; hg19: chr11-114427426;