chr6-46145150-A-G

Variant names:

• chr6-46145150-A-G
• rs3777632
• NM_014936.5:c.*1510A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014936.5(ENPP4):​c.*1510A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 377,258 control chromosomes in the GnomAD database, including 5,141 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 (1799 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3342 hom.)
• Consequence: ENPP4 NM_014936.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP4	NM_014936.5	MANE Select	c.*1510A>G		3_prime_UTR	Exon 4 of 4	NP_055751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP4	ENST00000321037.5	TSL:1 MANE Select	c.*1510A>G		3_prime_UTR	Exon 4 of 4	ENSP00000318066.3
	ENPP4	ENST00000962953.1		c.*1510A>G		3_prime_UTR	Exon 4 of 4	ENSP00000633012.1
	ENPP4	ENST00000962955.1		c.*1510A>G		3_prime_UTR	Exon 4 of 4	ENSP00000633014.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20097 AN: 151682 Hom.: 1800 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.166 AC: 37407 AN: 225458 Hom.: 3342 Cov.: 0 AF XY: 0.167 AC XY: 19114 AN XY: 114688

African (AFR) AF: 0.0314 AC: 208 AN: 6624

American (AMR) AF: 0.109 AC: 759 AN: 6942

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 2107 AN: 8556

East Asian (EAS) AF: 0.231 AC: 5009 AN: 21676

South Asian (SAS) AF: 0.365 AC: 750 AN: 2054

European-Finnish (FIN) AF: 0.156 AC: 2918 AN: 18714

Middle Eastern (MID) AF: 0.250 AC: 295 AN: 1182

European-Non Finnish (NFE) AF: 0.158 AC: 22851 AN: 144650

Other (OTH) AF: 0.167 AC: 2510 AN: 15060

GnomAD4 genome AF: 0.132 AC: 20096 AN: 151800 Hom.: 1799 Cov.: 32 AF XY: 0.136 AC XY: 10109 AN XY: 74222

African (AFR) AF: 0.0331 AC: 1375 AN: 41526

American (AMR) AF: 0.126 AC: 1916 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1465 AN: 5170

South Asian (SAS) AF: 0.323 AC: 1559 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1608 AN: 10600

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10734 AN: 67724

Other (OTH) AF: 0.145 AC: 306 AN: 2106

Alfa AF: 0.161 Hom.: 1278

Bravo AF: 0.121

Asia WGS AF: 0.310 AC: 1078 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		-0.15
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: rs3777632; hg19: chr6-46112887;