Genetic Variant ENPP4:c.-9G>A (chr6-46139575-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014936.5(ENPP4):c.-9G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,345,790 control chromosomes in the GnomAD database, including 20,705 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 0.13 ( 1793 hom., cov: 31)

Exomes 𝑓: 0.17 ( 18912 hom. )

Consequence

ENPP4
NM_014936.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.146

Publications

10 publications found

Variant links:

Genes affected

ENPP4 (HGNC:3359): (ectonucleotide pyrophosphatase/phosphodiesterase 4) Enables bis(5'-adenosyl)-triphosphatase activity. Involved in positive regulation of blood coagulation and purine ribonucleoside catabolic process. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENPP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP4	NM_014936.5 link	c.-9G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	ENST00000321037.5	NP_055751.1	Q9Y6X5
ENPP4	NM_014936.5 link	c.-9G>A		5_prime_UTR_variant	Exon 2 of 4	ENST00000321037.5	NP_055751.1	Q9Y6X5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP4	ENST00000321037.5 link	c.-9G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	1	NM_014936.5	ENSP00000318066.3		Q9Y6X5
ENPP4	ENST00000321037.5 link	c.-9G>A		5_prime_UTR_variant	Exon 2 of 4	1	NM_014936.5	ENSP00000318066.3		Q9Y6X5

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20096

AN:

151322

Hom.:

1793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.142

GnomAD2 exomes

AF:

0.173

AC:

42264

AN:

244884

AF XY:

0.182

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.0986

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.168

AC:

200327

AN:

1194348

Hom.:

18912

Cov.:

AF XY:

0.174

AC XY:

105463

AN XY:

607622

show subpopulations

African (AFR)

AF:

0.0278

AC:

778

AN:

28008

American (AMR)

AF:

0.101

AC:

4397

AN:

43578

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

5871

AN:

24260

East Asian (EAS)

AF:

0.245

AC:

9413

AN:

38426

South Asian (SAS)

AF:

0.323

AC:

25600

AN:

79368

European-Finnish (FIN)

AF:

0.148

AC:

7734

AN:

52282

Middle Eastern (MID)

AF:

0.236

AC:

1242

AN:

5256

European-Non Finnish (NFE)

AF:

0.157

AC:

136519

AN:

871870

Other (OTH)

AF:

0.171

AC:

8773

AN:

51300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

8401

16803

25204

33606

42007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4508

9016

13524

18032

22540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.133

AC:

20097

AN:

151442

Hom.:

1793

Cov.:

AF XY:

0.136

AC XY:

10083

AN XY:

73986

show subpopulations

African (AFR)

AF:

0.0344

AC:

1423

AN:

41406

American (AMR)

AF:

0.128

AC:

1933

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

824

AN:

3450

East Asian (EAS)

AF:

0.280

AC:

1444

AN:

5154

South Asian (SAS)

AF:

0.323

AC:

1553

AN:

4804

European-Finnish (FIN)

AF:

0.152

AC:

1594

AN:

10512

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10711

AN:

67654

Other (OTH)

AF:

0.148

AC:

310

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

820

1640

2461

3281

4101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

5097

Bravo

AF:

0.122

Asia WGS

AF:

0.305

AC:

1059

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

(source)

DANN

Benign

0.80

PhyloP100

-0.15

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over