rs11848070

Positions:

• chr14-71040884-G-A
• chr14-71040884-G-C
• chr14-71040884-G-T

Variant summary

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

The NM_014982.3(PCNX1):​c.3868-4249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 151,830 control chromosomes in the GnomAD database, including 52,830 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 0.83 (52830 hom., cov: 29)
• Consequence: PCNX1 NM_014982.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

Genes affected

PCNX1 (HGNC:19740): (pecanex 1) This gene encodes an evolutionarily conserved transmembrane protein similar to the pecanex protein in Drosophila. The fly protein is a component of the Notch signaling pathway, which functions in several developmental processes. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX1	NM_014982.3	c.3868-4249G>A		intron_variant		ENST00000304743.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX1	ENST00000304743.7	c.3868-4249G>A		intron_variant		1	NM_014982.3	P4
PCNX1	ENST00000439984.7	c.3535-4249G>A		intron_variant		1		A1
PCNX1	ENST00000554691.5	c.1044-4249G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125675 AN: 151712 Hom.: 52770 Cov.: 29

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.829 AC: 125793 AN: 151830 Hom.: 52830 Cov.: 29 AF XY: 0.829 AC XY: 61480 AN XY: 74148

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.841

Alfa AF: 0.779 Hom.: 60449

Bravo AF: 0.844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.72

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: rs11848070; hg19: chr14-71507601;