6-85489611-G-C

Variant names:

• chr6-85489611-G-C
• rs9450284
• NM_002526.4:c.1210+12G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002526.4(NT5E):​c.1210+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,585,018 control chromosomes in the GnomAD database, including 267,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (23113 hom., cov: 32)
  • Exomes 𝑓: 0.58 (243905 hom.)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -1.13
• Publications: 13 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-85489611-G-C is Benign according to our data. Variant chr6-85489611-G-C is described in ClinVar as Benign. ClinVar VariationId is 1174653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4	c.1210+12G>C		intron_variant	Intron 6 of 8	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.1210+12G>C		intron_variant	Intron 6 of 7		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.1210+12G>C		intron_variant	Intron 6 of 8	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369651.7	c.1210+12G>C		intron_variant	Intron 6 of 7	2		ENSP00000358665.3
NT5E	ENST00000416334.5	c.502+12G>C		intron_variant	Intron 4 of 4	3		ENSP00000414674.1
NT5E	ENST00000437581.1	c.295+12G>C		intron_variant	Intron 3 of 4	3		ENSP00000387630.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82354 AN: 151852 Hom.: 23093 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.572

GnomAD2 exomes AF: 0.606 AC: 149958 AN: 247272 AF XY: 0.610

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.790

Gnomad ASJ exome AF: 0.638

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.580 AC: 830558 AN: 1433048 Hom.: 243905 Cov.: 25 AF XY: 0.584 AC XY: 416957 AN XY: 714368

African (AFR) AF: 0.398 AC: 13052 AN: 32772

American (AMR) AF: 0.777 AC: 34593 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 16343 AN: 25854

East Asian (EAS) AF: 0.553 AC: 21808 AN: 39446

South Asian (SAS) AF: 0.721 AC: 61477 AN: 85216

European-Finnish (FIN) AF: 0.536 AC: 28525 AN: 53230

Middle Eastern (MID) AF: 0.676 AC: 3844 AN: 5688

European-Non Finnish (NFE) AF: 0.567 AC: 616158 AN: 1086950

Other (OTH) AF: 0.585 AC: 34758 AN: 59394

GnomAD4 genome AF: 0.542 AC: 82412 AN: 151970 Hom.: 23113 Cov.: 32 AF XY: 0.548 AC XY: 40667 AN XY: 74276

African (AFR) AF: 0.403 AC: 16722 AN: 41450

American (AMR) AF: 0.686 AC: 10473 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2192 AN: 3468

East Asian (EAS) AF: 0.549 AC: 2831 AN: 5156

South Asian (SAS) AF: 0.709 AC: 3410 AN: 4810

European-Finnish (FIN) AF: 0.542 AC: 5714 AN: 10548

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39012 AN: 67956

Other (OTH) AF: 0.575 AC: 1211 AN: 2106

Alfa AF: 0.514 Hom.: 2832

Bravo AF: 0.547

Asia WGS AF: 0.636 AC: 2211 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hereditary arterial and articular multiple calcification syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.44
PhyloP100		-1.1
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: rs9450284; hg19: chr6-86199329; COSMIC: COSV57629046;