Genetic Variant SLC14A2:p.Ala880Thr (chr18-45682394-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007163.4(SLC14A2):c.2638G>A(p.Ala880Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,613,370 control chromosomes in the GnomAD database, including 159,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14034 hom., cov: 31)

Exomes 𝑓: 0.44 ( 145474 hom. )

Consequence

SLC14A2
NM_007163.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Publications

32 publications found

Variant links:

Genes affected

SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

SLC14A2 links:

ENSG00000288545 (HGNC:):

ENSG00000288545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030146837).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A2	NM_007163.4 link	c.2638G>A	p.Ala880Thr	missense_variant	Exon 20 of 20	ENST00000255226.11	NP_009094.3	Q15849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11 link	c.2638G>A	p.Ala880Thr	missense_variant	Exon 20 of 20	1	NM_007163.4	ENSP00000255226.5		Q15849-1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64683

AN:

151712

Hom.:

14026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.435

GnomAD2 exomes

AF:

0.436

AC:

109677

AN:

251386

AF XY:

0.442

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.445

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.445

AC:

650075

AN:

1461540

Hom.:

145474

Cov.:

AF XY:

0.447

AC XY:

325110

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.381

AC:

12767

AN:

33476

American (AMR)

AF:

0.377

AC:

16839

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

12758

AN:

26134

East Asian (EAS)

AF:

0.401

AC:

15937

AN:

39698

South Asian (SAS)

AF:

0.493

AC:

42516

AN:

86252

European-Finnish (FIN)

AF:

0.442

AC:

23584

AN:

53416

Middle Eastern (MID)

AF:

0.487

AC:

2810

AN:

5766

European-Non Finnish (NFE)

AF:

0.446

AC:

495831

AN:

1111692

Other (OTH)

AF:

0.448

AC:

27033

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

21562

43124

64686

86248

107810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14922

29844

44766

59688

74610

<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:

0.426

AC:

64727

AN:

151830

Hom.:

14034

Cov.:

AF XY:

0.428

AC XY:

31749

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.380

AC:

15725

AN:

41384

American (AMR)

AF:

0.403

AC:

6156

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1697

AN:

3470

East Asian (EAS)

AF:

0.398

AC:

2048

AN:

5146

South Asian (SAS)

AF:

0.494

AC:

2371

AN:

4798

European-Finnish (FIN)

AF:

0.442

AC:

4644

AN:

10510

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30628

AN:

67952

Other (OTH)

AF:

0.432

AC:

910

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1902

3804

5706

7608

9510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.441

Hom.:

22990

Bravo

AF:

0.418

TwinsUK

AF:

0.451

AC:

1671

ALSPAC

AF:

0.443

AC:

1707

ESP6500AA

AF:

0.390

AC:

1720

ESP6500EA

AF:

0.450

AC:

3870

ExAC

AF:

0.436

AC:

52950

Asia WGS

AF:

0.432

AC:

1499

AN:

3478

EpiCase

AF:

0.456

EpiControl

AF:

0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.097

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.87

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

2.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.80

.;N

REVEL

Benign

0.062

Sift

Benign

0.41

.;T

Sift4G

Benign

0.34

T;T

Polyphen

0.017

B;B

Vest4

0.059

MPC

0.081

ClinPred

0.016

GERP RS

5.1

Varity_R

0.092

gMVP

0.83

Mutation Taster

=92/8

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

Computational scores

Splicing

Publications

Other links and lift over