rs11132226

Positions:

• chr4-184144142-G-A

Variant summary

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

The NM_153343.4(ENPP6):​c.421+9412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,192 control chromosomes in the GnomAD database, including 4,602 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 0.22 (4602 hom., cov: 34)
• Consequence: ENPP6 NM_153343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP6	NM_153343.4	c.421+9412C>T		intron_variant		ENST00000296741.7	NP_699174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP6	ENST00000296741.7	c.421+9412C>T		intron_variant		1	NM_153343.4	ENSP00000296741	P1
ENPP6	ENST00000512353.1	c.157+9412C>T		intron_variant		3		ENSP00000423497

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33611 AN: 152074 Hom.: 4589 Cov.: 34

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.221 AC: 33658 AN: 152192 Hom.: 4602 Cov.: 34 AF XY: 0.224 AC XY: 16682 AN XY: 74406

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.185

Alfa AF: 0.161 Hom.: 1969

Bravo AF: 0.227

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.28

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: rs11132226; hg19: chr4-185065295;