rs11132226

Variant names:

• chr4-184144142-G-A
• rs11132226
• NM_153343.4:c.421+9412C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP6	NM_153343.4	MANE Select	c.421+9412C>T		intron	N/A	NP_699174.1	Q6UWR7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP6	ENST00000296741.7	TSL:1 MANE Select	c.421+9412C>T		intron	N/A	ENSP00000296741.2	Q6UWR7
	ENPP6	ENST00000952351.1		c.242-19870C>T		intron	N/A	ENSP00000622410.1
	ENPP6	ENST00000512353.1	TSL:3	c.157+9412C>T		intron	N/A	ENSP00000423497.1	D6R9P1

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

African (AFR) AF: 0.384 AC: 15933 AN: 41502

American (AMR) AF: 0.191 AC: 2920 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5176

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2090 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9365 AN: 68002

Other (OTH) AF: 0.185 AC: 391 AN: 2114

Alfa AF: 0.161 Hom.: 3064

Bravo AF: 0.227

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.28
PhyloP100		0.035
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: rs11132226; hg19: chr4-185065295;