rs2242047

Variant names:

• chr15-84935465-C-T
• rs2242047
• NM_004213.5:c.1528C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-84935465-C-T
• chr15-84935465-C-A
• chr15-84935465-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004213.5(SLC28A1):​c.1528C>T​(p.Arg510Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0351 in 1,614,108 control chromosomes in the GnomAD database, including 3,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.051 (534 hom., cov: 32)
  • Exomes 𝑓: 0.033 (3459 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign; Affects no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 3.75
• Publications: 24 publications found

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031405985).
• BP6: Variant 15-84935465-C-T is Benign according to our data. Variant chr15-84935465-C-T is described in ClinVar as Benign|Affects. ClinVar VariationId is 634888.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004213.5. 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
	SLC28A1	NM_004213.5	MANE Select	c.1528C>T	p.Arg510Cys	missense	Exon 15 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.1528C>T	p.Arg510Cys	missense	Exon 14 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.1528C>T	p.Arg510Cys	missense	Exon 15 of 19	NP_001308651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.1528C>T	p.Arg510Cys	missense	Exon 15 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.1528C>T	p.Arg510Cys	missense	Exon 14 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000859184.1		c.1528C>T	p.Arg510Cys	missense	Exon 15 of 19	ENSP00000529243.1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7766 AN: 152168 Hom.: 536 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0294

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0493

GnomAD2 exomes AF: 0.0583 AC: 14656 AN: 251410 AF XY: 0.0580

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.0216

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.360

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.0160

Gnomad OTH exome AF: 0.0505

GnomAD4 exome AF: 0.0334 AC: 48872 AN: 1461822 Hom.: 3459 Cov.: 36 AF XY: 0.0347 AC XY: 25260 AN XY: 727210

African (AFR) AF: 0.0800 AC: 2680 AN: 33480

American (AMR) AF: 0.0231 AC: 1031 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 1612 AN: 26134

East Asian (EAS) AF: 0.350 AC: 13905 AN: 39698

South Asian (SAS) AF: 0.0916 AC: 7899 AN: 86256

European-Finnish (FIN) AF: 0.0128 AC: 681 AN: 53388

Middle Eastern (MID) AF: 0.0397 AC: 229 AN: 5768

European-Non Finnish (NFE) AF: 0.0159 AC: 17720 AN: 1111978

Other (OTH) AF: 0.0516 AC: 3115 AN: 60396

GnomAD4 genome AF: 0.0510 AC: 7770 AN: 152286 Hom.: 534 Cov.: 32 AF XY: 0.0538 AC XY: 4008 AN XY: 74444

African (AFR) AF: 0.0831 AC: 3453 AN: 41542

American (AMR) AF: 0.0293 AC: 449 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5168

South Asian (SAS) AF: 0.0935 AC: 452 AN: 4832

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1033 AN: 68028

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0310 Hom.: 1009

Bravo AF: 0.0536

TwinsUK AF: 0.0151 AC: 56

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.0853 AC: 376

ESP6500EA AF: 0.0174 AC: 150

ExAC AF: 0.0590 AC: 7159

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign; Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC28A1-related disorder (1)
-	-	-	Uridine-cytidineuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.17
MPC		0.51
ClinPred		0.035	T
GERP RS		4.1
Varity_R		0.14
gMVP		0.59
Mutation Taster		=82/18	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: rs2242047; hg19: chr15-85478696; COSMIC: COSV54477526; COSMIC: COSV54477526;