6-85485580-A-G

Variant names:

• chr6-85485580-A-G
• rs9450282
• NM_002526.4:c.949+148A>G

Variant summary

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

The NM_002526.4(NT5E):​c.949+148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 809,736 control chromosomes in the GnomAD database, including 166,349 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 0.63 (30905 hom., cov: 32)
  • Exomes 𝑓: 0.64 (135444 hom.)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 14 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 = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4	c.949+148A>G		intron_variant	Intron 4 of 8	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.949+148A>G		intron_variant	Intron 4 of 7		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.949+148A>G		intron_variant	Intron 4 of 8	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369651.7	c.949+148A>G		intron_variant	Intron 4 of 7	2		ENSP00000358665.3
NT5E	ENST00000416334.5	c.241+148A>G		intron_variant	Intron 2 of 4	3		ENSP00000414674.1
NT5E	ENST00000437581.1	c.34+148A>G		intron_variant	Intron 1 of 4	3		ENSP00000387630.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96269 AN: 151914 Hom.: 30884 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.635 AC: 417773 AN: 657702 Hom.: 135444 AF XY: 0.636 AC XY: 221144 AN XY: 347644

African (AFR) AF: 0.605 AC: 10268 AN: 16976

American (AMR) AF: 0.722 AC: 23493 AN: 32548

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 13319 AN: 19496

East Asian (EAS) AF: 0.364 AC: 11795 AN: 32390

South Asian (SAS) AF: 0.664 AC: 40889 AN: 61596

European-Finnish (FIN) AF: 0.603 AC: 21261 AN: 35232

Middle Eastern (MID) AF: 0.691 AC: 2415 AN: 3494

European-Non Finnish (NFE) AF: 0.646 AC: 272662 AN: 422276

Other (OTH) AF: 0.643 AC: 21671 AN: 33694

GnomAD4 genome AF: 0.634 AC: 96345 AN: 152034 Hom.: 30905 Cov.: 32 AF XY: 0.632 AC XY: 46932 AN XY: 74290

African (AFR) AF: 0.609 AC: 25246 AN: 41478

American (AMR) AF: 0.704 AC: 10761 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2338 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2005 AN: 5168

South Asian (SAS) AF: 0.658 AC: 3167 AN: 4810

European-Finnish (FIN) AF: 0.611 AC: 6435 AN: 10538

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44130 AN: 67978

Other (OTH) AF: 0.633 AC: 1335 AN: 2110

Alfa AF: 0.649 Hom.: 17769

Bravo AF: 0.640

Asia WGS AF: 0.534 AC: 1857 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		0.71
PromoterAI		0.024	Neutral
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: rs9450282; hg19: chr6-86195298; COSMIC: COSV57629173;