rs17075469

chr4-184204857-G-C

Variant summary

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

The NM_153343.4(ENPP6):c.241+12722C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,252 control chromosomes in the GnomAD database, including 809 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 0.093 (809 hom., cov: 33)
• Consequence: ENPP6 NM_153343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

Genes affected

ENPP6 (HGNC:23409): (ectonucleotide pyrophosphatase/phosphodiesterase 6) Enables glycerophosphocholine cholinephosphodiesterase activity. Involved in choline metabolic process and lipid metabolic process. Located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP6	NM_153343.4	c.241+12722C>G		intron_variant		ENST00000296741.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENPP6	ENST00000296741.7	c.241+12722C>G		intron_variant		1	NM_153343.4	P1
ENPP6	ENST00000512353.1	c.-170-732C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14140 AN: 152134 Hom.: 811 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0929 AC: 14147 AN: 152252 Hom.: 809 Cov.: 33 AF XY: 0.0937 AC XY: 6972 AN XY: 74442

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0823

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.0368

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0768 Hom.: 62

Bravo AF: 0.0937

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.0
Dann	Benign	0.35

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: rs17075469; hg19: chr4-185126010;