dbSNP rs2290272: SLC28A1:p.Val189Ile (chr15-84904200-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004213.5(SLC28A1):c.565G>A(p.Val189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,613,866 control chromosomes in the GnomAD database, including 118,329 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9369 hom., cov: 33)

Exomes 𝑓: 0.38 ( 108960 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.852

Publications

47 publications found

Variant links:

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]

SLC28A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.0749636E-5).

BP6

Variant 15-84904200-G-A is Benign according to our data. Variant chr15-84904200-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059692.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.565G>A	p.Val189Ile	missense_variant	Exon 7 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC28A1	ENST00000394573.6 link	c.565G>A	p.Val189Ile	missense_variant	Exon 7 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3 link	c.565G>A	p.Val189Ile	missense_variant	Exon 6 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000538177.5 link	c.565G>A	p.Val189Ile	missense_variant	Exon 6 of 15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51482

AN:

151998

Hom.:

9354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.403

AC:

101384

AN:

251380

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.400

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.381

AC:

556305

AN:

1461750

Hom.:

108960

Cov.:

AF XY:

0.385

AC XY:

279657

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.204

AC:

6831

AN:

33480

American (AMR)

AF:

0.567

AC:

25353

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

8176

AN:

26136

East Asian (EAS)

AF:

0.401

AC:

15929

AN:

39700

South Asian (SAS)

AF:

0.524

AC:

45186

AN:

86258

European-Finnish (FIN)

AF:

0.406

AC:

21632

AN:

53318

Middle Eastern (MID)

AF:

0.353

AC:

2038

AN:

5768

European-Non Finnish (NFE)

AF:

0.368

AC:

408959

AN:

1111978

Other (OTH)

AF:

0.368

AC:

22201

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

23208

46416

69624

92832

116040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13248

26496

39744

52992

66240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.339

AC:

51522

AN:

152116

Hom.:

9369

Cov.:

AF XY:

0.346

AC XY:

25710

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.217

AC:

9010

AN:

41514

American (AMR)

AF:

0.462

AC:

7062

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1097

AN:

3470

East Asian (EAS)

AF:

0.393

AC:

2033

AN:

5168

South Asian (SAS)

AF:

0.554

AC:

2671

AN:

4822

European-Finnish (FIN)

AF:

0.408

AC:

4313

AN:

10574

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24352

AN:

67958

Other (OTH)

AF:

0.328

AC:

692

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1751

3502

5254

7005

8756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.349

Hom.:

41407

Bravo

AF:

0.334

TwinsUK

AF:

0.374

AC:

1387

ALSPAC

AF:

0.378

AC:

1458

ESP6500AA

AF:

0.218

AC:

962

ESP6500EA

AF:

0.350

AC:

3013

ExAC

AF:

0.391

AC:

47489

Asia WGS

AF:

0.439

AC:

1525

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.353

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0030

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0050

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.087

T;T;.

MetaRNN

Benign

0.000021

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.45

.;N;N

PhyloP100

-0.85

PrimateAI

Benign

0.44

PROVEAN

Benign

0.44

N;N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.035

B;B;B

Vest4

0.037

MPC

0.063

ClinPred

0.0021

GERP RS

-5.9

Varity_R

0.030

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over