rs201567504

Variant names:

• chr2-18576305-C-T
• rs201567504
• NM_033253.4:c.1208G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_033253.4(NT5C1B):​c.1208G>A​(p.Arg403His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: NT5C1B NM_033253.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 6 publications found

Genes affected

NT5C1B (HGNC:17818): (5'-nucleotidase, cytosolic IB) Cytosolic 5-prime nucleotidases, such as NT5C1B, catalyze production of adenosine, which regulates diverse physiologic processes (Sala-Newby and Newby, 2001 [PubMed 11690631]).[supplied by OMIM, Mar 2008]

NT5C1B-RDH14 (HGNC:38831): (NT5C1B-RDH14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NT5C1B (5'-nucleotidase, cytosolic IB) and RDH14 (retinol dehydrogenase 14) genes on chromosome 2. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

ENSG00000304698 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1B	NM_033253.4	MANE Select	c.1208G>A	p.Arg403His	missense	Exon 8 of 9	NP_150278.2	Q96P26-2
	NT5C1B-RDH14	NM_001199103.2		c.1214G>A	p.Arg405His	missense	Exon 8 of 9	NP_001186032.1
	NT5C1B	NM_001199087.2		c.1439G>A	p.Arg480His	missense	Exon 9 of 10	NP_001186016.1	B4DZ86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1B	ENST00000304081.9	TSL:1 MANE Select	c.1208G>A	p.Arg403His	missense	Exon 8 of 9	ENSP00000305979.4	Q96P26-2
	NT5C1B	ENST00000359846.6	TSL:1	c.1388G>A	p.Arg463His	missense	Exon 9 of 10	ENSP00000352904.2	Q96P26-1
	NT5C1B-RDH14	ENST00000532967.5	TSL:2	c.1388G>A	p.Arg463His	missense	Exon 9 of 11	ENSP00000433415.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251218 AF XY: 0.0000884

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727098

African (AFR) AF: 0.0000598 AC: 2 AN: 33460

American (AMR) AF: 0.0000672 AC: 3 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111824

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.0000483 AC: 2 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000384 AC: 2 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.9
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.97
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.89		Gain of sheet (P = 0.1208)
MVP		0.89
MPC		0.75
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.55
gMVP		0.87
Mutation Taster		=50/50

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: rs201567504; hg19: chr2-18757571; COSMIC: COSV58397396;