rs17075469

Variant names:

• chr4-184204857-G-C
• rs17075469
• NM_153343.4:c.241+12722C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

ENSG00000295598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.241+12722C>G		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.241+12722C>G		intron	N/A	ENSP00000296741.2	Q6UWR7
	ENPP6	ENST00000952351.1		c.241+12722C>G		intron	N/A	ENSP00000622410.1
	ENPP6	ENST00000512353.1	TSL:3	c.-170-732C>G		intron	N/A	ENSP00000423497.1	D6R9P1

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

African (AFR) AF: 0.137 AC: 5700 AN: 41518

American (AMR) AF: 0.0823 AC: 1259 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3468

East Asian (EAS) AF: 0.0368 AC: 191 AN: 5194

South Asian (SAS) AF: 0.186 AC: 895 AN: 4824

European-Finnish (FIN) AF: 0.0454 AC: 481 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4974 AN: 68028

Other (OTH) AF: 0.115 AC: 242 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.35
PhyloP100		0.57
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17075469;

hg19: chr4-185126010;

Mutation Effect Viewer