dbSNP rs11877062: SLC14A1:c.-22+2268C>T (chr18-45727281-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_001128588.4(SLC14A1):c.10C>T(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,550,698 control chromosomes in the GnomAD database, including 178,705 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.42 ( 14177 hom., cov: 33)

Exomes 𝑓: 0.48 ( 164528 hom. )

Consequence

SLC14A1
NM_001128588.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.597

Publications

30 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 Gene-Disease associations (from GenCC):

blood group, kidd system
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8799644E-4).

BP6

Variant 18-45727281-C-T is Benign according to our data. Variant chr18-45727281-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060924.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC14A1	NM_015865.7	MANE Select	c.-22+2268C>T		intron	N/A	NP_056949.4	Q13336-1
SLC14A1	NM_001128588.4		c.10C>T	p.Arg4Trp	missense	Exon 3 of 11	NP_001122060.3	Q13336-2
SLC14A1	NM_001146037.1		c.10C>T	p.Arg4Trp	missense	Exon 1 of 9	NP_001139509.1	Q13336-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC14A1	ENST00000321925.9	TSL:1 MANE Select	c.-22+2268C>T	intron	N/A	ENSP00000318546.4	Q13336-1
SLC14A1	ENST00000535474.5	TSL:1	c.-56+2268C>T	intron	N/A	ENSP00000441998.1	F5GWS2
SLC14A1	ENST00000899337.1		c.-159C>T	5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	ENSP00000569396.1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63251

AN:

151970

Hom.:

14179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.443

GnomAD2 exomes

AF:

0.474

AC:

73007

AN:

153972

AF XY:

0.472

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.512

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.495

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.482

AC:

674572

AN:

1398610

Hom.:

164528

Cov.:

AF XY:

0.481

AC XY:

331592

AN XY:

689858

show subpopulations

African (AFR)

AF:

0.228

AC:

7197

AN:

31588

American (AMR)

AF:

0.512

AC:

18286

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

11287

AN:

25174

East Asian (EAS)

AF:

0.542

AC:

19383

AN:

35738

South Asian (SAS)

AF:

0.431

AC:

34109

AN:

79216

European-Finnish (FIN)

AF:

0.499

AC:

24561

AN:

49242

Middle Eastern (MID)

AF:

0.405

AC:

2293

AN:

5660

European-Non Finnish (NFE)

AF:

0.492

AC:

530588

AN:

1078326

Other (OTH)

AF:

0.464

AC:

26868

AN:

57966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

17966

35932

53898

71864

89830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15626

31252

46878

62504

78130

<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:

0.416

AC:

63259

AN:

152088

Hom.:

14177

Cov.:

AF XY:

0.415

AC XY:

30842

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.234

AC:

9701

AN:

41506

American (AMR)

AF:

0.476

AC:

7287

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1550

AN:

3466

East Asian (EAS)

AF:

0.518

AC:

2671

AN:

5160

South Asian (SAS)

AF:

0.414

AC:

1997

AN:

4822

European-Finnish (FIN)

AF:

0.489

AC:

5163

AN:

10568

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.493

AC:

33500

AN:

67956

Other (OTH)

AF:

0.441

AC:

932

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1842

3685

5527

7370

9212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.449

Hom.:

21928

Bravo

AF:

0.409

TwinsUK

AF:

0.481

AC:

1784

ALSPAC

AF:

0.489

AC:

1886

ESP6500AA

AF:

0.212

AC:

293

ESP6500EA

AF:

0.492

AC:

1567

ExAC

AF:

0.416

AC:

9149

Asia WGS

AF:

0.430

AC:

1500

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC14A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

MetaRNN

Benign

0.00039

MetaSVM

Benign

-0.91

PhyloP100

0.60

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

REVEL

Benign

0.084

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.074

MPC

0.11

ClinPred

0.019

GERP RS

2.8

PromoterAI

-0.14

Neutral

(source)

gMVP

0.12

Mutation Taster

=300/0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over