chr6-85449425-A-G

Variant names:

• chr6-85449425-A-G
• rs2065114
• ENST00000369651.7:c.-715A>G

Variant summary

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

The ENST00000369651.7(NT5E):​c.-715A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,026 control chromosomes in the GnomAD database, including 45,878 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 0.77 (45878 hom., cov: 31)
• Consequence: NT5E ENST00000369651.7 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 7 publications found

Genes affected

NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

NT5E Gene-Disease associations (from GenCC):

• hereditary arterial and articular multiple calcification syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

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 = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000369651.7	c.-715A>G		upstream_gene_variant		2		ENSP00000358665.3

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116334 AN: 151906 Hom.: 45813 Cov.: 31

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.766 AC: 116463 AN: 152026 Hom.: 45878 Cov.: 31 AF XY: 0.766 AC XY: 56878 AN XY: 74266

African (AFR) AF: 0.942 AC: 39112 AN: 41522

American (AMR) AF: 0.826 AC: 12629 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2656 AN: 3468

East Asian (EAS) AF: 0.605 AC: 3117 AN: 5152

South Asian (SAS) AF: 0.831 AC: 3989 AN: 4800

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10530

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45865 AN: 67952

Other (OTH) AF: 0.761 AC: 1608 AN: 2112

Alfa AF: 0.738 Hom.: 10269

Bravo AF: 0.788

Asia WGS AF: 0.745 AC: 2588 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	8.0
DANN	Benign	0.63
PhyloP100		0.0090
PromoterAI		-0.073	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2065114; hg19: chr6-86159143;