chr2-18563831-C-T

Variant names:

• chr2-18563831-C-T
• rs1271872801
• NM_033253.4:c.1618G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_033253.4(NT5C1B):​c.1618G>A​(p.Ala540Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,435,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: NT5C1B NM_033253.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11038351).
• BP6: Variant 2-18563831-C-T is Benign according to our data. Variant chr2-18563831-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2205311.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1618G>A	p.Ala540Thr	missense	Exon 9 of 9	NP_150278.2	Q96P26-2
	NT5C1B	NM_001199087.2		c.1849G>A	p.Ala617Thr	missense	Exon 10 of 10	NP_001186016.1	B4DZ86
	NT5C1B	NM_001199088.2		c.1804G>A	p.Ala602Thr	missense	Exon 10 of 10	NP_001186017.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1B	ENST00000304081.9	TSL:1 MANE Select	c.1618G>A	p.Ala540Thr	missense	Exon 9 of 9	ENSP00000305979.4	Q96P26-2
	NT5C1B	ENST00000359846.6	TSL:1	c.1798G>A	p.Ala600Thr	missense	Exon 10 of 10	ENSP00000352904.2	Q96P26-1
	NT5C1B-RDH14	ENST00000532967.5	TSL:2	c.1784+14G>A		intron	N/A	ENSP00000433415.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000420 AC: 1 AN: 238152 AF XY: 0.00000775

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000915

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000766 AC: 11 AN: 1435252 Hom.: 0 Cov.: 30 AF XY: 0.00000844 AC XY: 6 AN XY: 711154

African (AFR) AF: 0.0000620 AC: 2 AN: 32280

American (AMR) AF: 0.00 AC: 0 AN: 40926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39226

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00000729 AC: 8 AN: 1096766

Other (OTH) AF: 0.00 AC: 0 AN: 58976

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.073
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.055
DANN	Benign	0.63
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.48
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.43
Sift	Benign	0.93	T
Sift4G	Benign	0.48	T
Polyphen		0.16	B
Vest4		0.044
MutPred		0.68		Loss of catalytic residue at A600 (P = 0.0714)
MVP		0.061
MPC		0.21
ClinPred		0.088	T
GERP RS		-8.8
Varity_R		0.023
gMVP		0.65
Mutation Taster		=90/10	polymorphism

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: rs1271872801; hg19: chr2-18745097; COSMIC: COSV58398330; COSMIC: COSV58398330;