rs4431401

chr6-85479802-T-C

Variant summary

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

The NM_002526.4(NT5E):c.752-5433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,948 control chromosomes in the GnomAD database, including 17,800 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 0.46 (17800 hom., cov: 31)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4	c.752-5433T>C		intron_variant		ENST00000257770.8
NT5E	NM_001204813.2	c.752-5433T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8	c.752-5433T>C		intron_variant		1	NM_002526.4	P1
NT5E	ENST00000369651.7	c.752-5433T>C		intron_variant		2
NT5E	ENST00000416334.5	c.46-5433T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70521 AN: 151832 Hom.: 17786 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.464 AC: 70561 AN: 151948 Hom.: 17800 Cov.: 31 AF XY: 0.466 AC XY: 34574 AN XY: 74250

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.484

Alfa AF: 0.504 Hom.: 3644

Bravo AF: 0.462

Asia WGS AF: 0.443 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.80
Dann	Benign	0.46

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: rs4431401; hg19: chr6-86189520;