6-85490431-C-T

Position:

• chr6-85490431-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002526.4(NT5E):​c.1211-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,527,280 control chromosomes in the GnomAD database, including 267 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 0.014 (28 hom., cov: 33)
  • Exomes 𝑓: 0.018 (239 hom.)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0139 (2110/152334) while in subpopulation NFE AF= 0.021 (1426/68022). AF 95% confidence interval is 0.0201. There are 28 homozygotes in gnomad4. There are 1009 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4	c.1211-77C>T		intron_variant		ENST00000257770.8
NT5E	NM_001204813.2	c.1210+832C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8	c.1211-77C>T		intron_variant		1	NM_002526.4	P1
NT5E	ENST00000369651.7	c.1210+832C>T		intron_variant		2
NT5E	ENST00000416334.5	c.504+832C>T		intron_variant		3
NT5E	ENST00000437581.1	c.298-77C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2108 AN: 152216 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0175 AC: 24116 AN: 1374946 Hom.: 239 AF XY: 0.0175 AC XY: 12077 AN XY: 689102

Gnomad4 AFR exome AF: 0.00277

Gnomad4 AMR exome AF: 0.00673

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.00687

Gnomad4 FIN exome AF: 0.0225

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0139 AC: 2110 AN: 152334 Hom.: 28 Cov.: 33 AF XY: 0.0135 AC XY: 1009 AN XY: 74496

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00678 Hom.: 2

Bravo AF: 0.0126

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.42

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: rs41271619; hg19: chr6-86200149;