dbSNP rs6919558: NT5E:c.-482G>A (chr6-85449658-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000369651.7(NT5E):c.-482G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 156,802 control chromosomes in the GnomAD database, including 48 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 0.013 ( 48 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

NT5E
ENST00000369651.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.340

Publications

2 publications found

Variant links:

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

NT5E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1968/152220) while in subpopulation AFR AF = 0.0452 (1876/41522). AF 95% confidence interval is 0.0435. There are 48 homozygotes in GnomAd4. There are 928 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

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 link	c.-482G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	2		ENSP00000358665.3		P21589-2
NT5E	ENST00000369651.7 link	c.-482G>A		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000358665.3		P21589-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1965

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00622

GnomAD4 exome

AF:

0.000655

AC:

AN:

4582

Hom.:

Cov.:

AF XY:

0.000978

AC XY:

AN XY:

2046

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

114

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3562

Other (OTH)

AF:

0.00

AC:

AN:

362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.642

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0129

AC:

1968

AN:

152220

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0452

AC:

1876

AN:

41522

American (AMR)

AF:

0.00464

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68012

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

187

281

374

468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00814

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.7

(source)

DANN

Benign

0.78

PhyloP100

0.34

PromoterAI

-0.026

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over