6-85487272-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002526.4(NT5E):c.950-63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,393,284 control chromosomes in the GnomAD database, including 11,065 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 0.17 (2982 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8083 hom.)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4	c.950-63C>G		intron_variant		ENST00000257770.8
NT5E	NM_001204813.2	c.950-63C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8	c.950-63C>G		intron_variant		1	NM_002526.4	P1
NT5E	ENST00000369651.7	c.950-63C>G		intron_variant		2
NT5E	ENST00000416334.5	c.244-63C>G		intron_variant		3
NT5E	ENST00000437581.1	c.37-63C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25288 AN: 152030 Hom.: 2979 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.106 AC: 131878 AN: 1241136 Hom.: 8083 AF XY: 0.106 AC XY: 66759 AN XY: 628950

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.0741

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0527

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0889

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.166 AC: 25309 AN: 152148 Hom.: 2982 Cov.: 33 AF XY: 0.163 AC XY: 12094 AN XY: 74392

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0528

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0885

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0450 Hom.: 45

Bravo AF: 0.174

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	7.5
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs3812139; hg19: chr6-86196990;