Variant chr18-45682394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC14A2	NM_007163.4 link	c.2638G>A	p.Ala880Thr	missense_variant	20/20	ENST00000255226.11	NP_009094.3	Q15849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC14A2	ENST00000255226.11 link	c.2638G>A	p.Ala880Thr	missense_variant	20/20	1	NM_007163.4	ENSP00000255226.5	Q15849-1
SLC14A2	ENST00000586448.5 link	c.2638G>A	p.Ala880Thr	missense_variant	21/21	2		ENSP00000465953.1	Q15849-1
ENSG00000288545	ENST00000589510.5 link	n.206+10001C>T		intron_variant		5

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

GnomAD3 exomes

AF:

0.436

AC:

109677

AN:

251386

Hom.:

24384

AF XY:

0.442

AC XY:

59986

AN XY:

135864

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 SAS exome

AF:

0.499

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

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.442

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.426

AC:

64727

AN:

151830

Hom.:

14034

Cov.:

AF XY:

0.428

AC XY:

31749

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.443

Hom.:

18151

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over