rs4431401

Variant names:

• chr6-85479802-T-C
• rs4431401
• NM_002526.4:c.752-5433T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.87).
• 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 rank	MANE	Protein	UniProt
NT5E	NM_002526.4	c.752-5433T>C		intron_variant	Intron 3 of 8	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.752-5433T>C		intron_variant	Intron 3 of 7		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.752-5433T>C		intron_variant	Intron 3 of 8	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369651.7	c.752-5433T>C		intron_variant	Intron 3 of 7	2		ENSP00000358665.3
NT5E	ENST00000416334.5	c.44-5433T>C		intron_variant	Intron 1 of 4	3		ENSP00000414674.1

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

African (AFR) AF: 0.260 AC: 10789 AN: 41460

American (AMR) AF: 0.587 AC: 8968 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1727 AN: 5166

South Asian (SAS) AF: 0.536 AC: 2576 AN: 4806

European-Finnish (FIN) AF: 0.523 AC: 5505 AN: 10530

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37258 AN: 67934

Other (OTH) AF: 0.484 AC: 1021 AN: 2108

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
PhyloP100		-0.37
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: rs4431401; hg19: chr6-86189520;