dbSNP rs2242046: SLC28A1:p.Asp521Asn (chr15-84935498-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.1561G>A(p.Asp521Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,130 control chromosomes in the GnomAD database, including 169,648 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 0.35 ( 11846 hom., cov: 33)

Exomes 𝑓: 0.45 ( 157802 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.02

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=3.5131863E-5).

BP6

Variant 15-84935498-G-A is Benign according to our data. Variant chr15-84935498-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059229.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.1561G>A	p.Asp521Asn	missense_variant	Exon 15 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC28A1	ENST00000394573.6 link	c.1561G>A	p.Asp521Asn	missense_variant	Exon 15 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3 link	c.1561G>A	p.Asp521Asn	missense_variant	Exon 14 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000538177.5 link	c.1084-7947G>A		intron_variant	Intron 11 of 14	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52685

AN:

152016

Hom.:

11854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0959

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.0775

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.388

GnomAD2 exomes

AF:

0.374

AC:

93823

AN:

250790

AF XY:

0.387

show subpopulations

Gnomad AFR exome

AF:

0.0851

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.0750

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

AF:

0.450

AC:

657428

AN:

1460996

Hom.:

157802

Cov.:

AF XY:

0.449

AC XY:

326253

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.0854

AC:

2858

AN:

33476

American (AMR)

AF:

0.219

AC:

9812

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

14631

AN:

26136

East Asian (EAS)

AF:

0.0673

AC:

2673

AN:

39696

South Asian (SAS)

AF:

0.313

AC:

27029

AN:

86238

European-Finnish (FIN)

AF:

0.452

AC:

23932

AN:

52968

Middle Eastern (MID)

AF:

0.572

AC:

3297

AN:

5768

European-Non Finnish (NFE)

AF:

0.492

AC:

547221

AN:

1111610

Other (OTH)

AF:

0.430

AC:

25975

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

18880

37760

56641

75521

94401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15416

30832

46248

61664

77080

<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:

0.346

AC:

52660

AN:

152134

Hom.:

11846

Cov.:

AF XY:

0.340

AC XY:

25324

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0957

AC:

3975

AN:

41542

American (AMR)

AF:

0.288

AC:

4411

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1953

AN:

3470

East Asian (EAS)

AF:

0.0773

AC:

400

AN:

5176

South Asian (SAS)

AF:

0.292

AC:

1406

AN:

4822

European-Finnish (FIN)

AF:

0.444

AC:

4702

AN:

10582

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34224

AN:

67942

Other (OTH)

AF:

0.383

AC:

805

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1547

3095

4642

6190

7737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.454

Hom.:

84587

Bravo

AF:

0.323

TwinsUK

AF:

0.489

AC:

1814

ALSPAC

AF:

0.479

AC:

1846

ESP6500AA

AF:

0.103

AC:

456

ESP6500EA

AF:

0.498

AC:

4278

ExAC

AF:

0.375

AC:

45541

Asia WGS

AF:

0.147

AC:

513

AN:

3478

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

0.066

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0069

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.18

T;.

MetaRNN

Benign

0.000035

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.45

N;N

PhyloP100

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.0080

Sift

Benign

0.13

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.025

B;B

Vest4

0.030

MPC

0.075

ClinPred

0.017

GERP RS

-0.14

Varity_R

0.041

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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