chr18-45739554-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015865.7(SLC14A1):c.838G>A(p.Asp280Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,474 control chromosomes in the GnomAD database, including 180,070 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 14195 hom., cov: 31)

Exomes 𝑓: 0.47 ( 165875 hom. )

Consequence

SLC14A1
NM_015865.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.723

Publications

83 publications found

Variant links:

Genes affected

SLC14A1 (HGNC:10918): (solute carrier family 14 member 1 (Kidd blood group)) The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]

SLC14A1 links:

ENSG00000288545 (HGNC:):

ENSG00000288545 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9844046E-4).

BP6

Variant 18-45739554-G-A is Benign according to our data. Variant chr18-45739554-G-A is described in ClinVar as Benign. ClinVar VariationId is 17717.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015865.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC14A1	NM_015865.7	MANE Select	c.838G>A	p.Asp280Asn	missense	Exon 8 of 10	NP_056949.4
SLC14A1	NM_001128588.4		c.1006G>A	p.Asp336Asn	missense	Exon 9 of 11	NP_001122060.3
SLC14A1	NM_001146037.1		c.1006G>A	p.Asp336Asn	missense	Exon 7 of 9	NP_001139509.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC14A1	ENST00000321925.9	TSL:1 MANE Select	c.838G>A	p.Asp280Asn	missense	Exon 8 of 10	ENSP00000318546.4
SLC14A1	ENST00000586142.5	TSL:1	c.838G>A	p.Asp280Asn	missense	Exon 6 of 8	ENSP00000470476.1
SLC14A1	ENST00000535474.5	TSL:1	c.442G>A	p.Asp148Asn	missense	Exon 6 of 8	ENSP00000441998.1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63870

AN:

151798

Hom.:

14196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.471

AC:

118542

AN:

251432

AF XY:

0.472

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.515

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.536

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.489

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.474

AC:

693015

AN:

1461558

Hom.:

165875

Cov.:

AF XY:

0.473

AC XY:

343901

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.265

AC:

8882

AN:

33472

American (AMR)

AF:

0.515

AC:

23046

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

11316

AN:

26136

East Asian (EAS)

AF:

0.540

AC:

21451

AN:

39700

South Asian (SAS)

AF:

0.428

AC:

36948

AN:

86254

European-Finnish (FIN)

AF:

0.490

AC:

26183

AN:

53416

Middle Eastern (MID)

AF:

0.409

AC:

2360

AN:

5768

European-Non Finnish (NFE)

AF:

0.481

AC:

535245

AN:

1111706

Other (OTH)

AF:

0.457

AC:

27584

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

22438

44877

67315

89754

112192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15676

31352

47028

62704

78380

<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:

0.421

AC:

63882

AN:

151916

Hom.:

14195

Cov.:

AF XY:

0.419

AC XY:

31078

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.269

AC:

11151

AN:

41426

American (AMR)

AF:

0.477

AC:

7288

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1479

AN:

3466

East Asian (EAS)

AF:

0.518

AC:

2666

AN:

5144

South Asian (SAS)

AF:

0.406

AC:

1953

AN:

4810

European-Finnish (FIN)

AF:

0.479

AC:

5062

AN:

10562

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32890

AN:

67918

Other (OTH)

AF:

0.444

AC:

934

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1837

3674

5510

7347

9184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.464

Hom.:

65920

Bravo

AF:

0.415

TwinsUK

AF:

0.472

AC:

1751

ALSPAC

AF:

0.477

AC:

1839

ESP6500AA

AF:

0.265

AC:

1169

ESP6500EA

AF:

0.486

AC:

4177

ExAC

AF:

0.469

AC:

56994

Asia WGS

AF:

0.428

AC:

1494

AN:

3478

EpiCase

AF:

0.478

EpiControl

AF:

0.480

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

SLC14A1-related disorder

Benign:1

Oct 17, 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).

KIDD BLOOD POLYMORPHISM Jk(a)/Jk(b)

Benign:1

Jul 01, 1997

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.9

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.025

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.17

MetaRNN

Benign

0.00030

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.72

PhyloP100

0.72

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.22

REVEL

Benign

0.061

Sift

Benign

0.59

Sift4G

Benign

0.64

Polyphen

0.0010

Vest4

0.026

MPC

0.10

ClinPred

0.0025

GERP RS

-7.6

Varity_R

0.079

gMVP

0.61

Mutation Taster

=296/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over