rs11568482

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004254.4(SLC22A8):c.913A>T(p.Ile305Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,018 control chromosomes in the GnomAD database, including 57 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 0.0024 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 50 hom. )

Consequence

SLC22A8
NM_004254.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.498

Publications

19 publications found

Variant links:

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

SLC22A8 links:

ENSG00000301851 (HGNC:):

ENSG00000301851 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020394623).

BP6

Variant 11-62995792-T-A is Benign according to our data. Variant chr11-62995792-T-A is described in ClinVar as Benign. ClinVar VariationId is 1232453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00236 (359/152198) while in subpopulation EAS AF = 0.0531 (274/5164). AF 95% confidence interval is 0.0479. There are 7 homozygotes in GnomAd4. There are 203 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4 link	c.913A>T	p.Ile305Phe	missense_variant	Exon 7 of 11	ENST00000336232.7	NP_004245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7 link	c.913A>T	p.Ile305Phe	missense_variant	Exon 7 of 11	1	NM_004254.4	ENSP00000337335.2

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0527

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00471

AC:

1184

AN:

251356

AF XY:

0.00448

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.0591

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00158

AC:

2308

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1129

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33478

American (AMR)

AF:

0.00145

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

26132

East Asian (EAS)

AF:

0.0474

AC:

1880

AN:

39700

South Asian (SAS)

AF:

0.000707

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000558

AC:

AN:

1111962

Other (OTH)

AF:

0.00328

AC:

198

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

125

250

374

499

624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00236

AC:

359

AN:

152198

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.000915

AC:

AN:

41538

American (AMR)

AF:

0.00150

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0531

AC:

274

AN:

5164

South Asian (SAS)

AF:

0.00291

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00174

Hom.:

Bravo

AF:

0.00282

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00441

AC:

535

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23649425)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.24

T;.;.;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.0

.;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;.;.;.;M

PhyloP100

0.50

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.20

T;T;D;T;T

Vest4

0.13

ClinPred

0.0083

GERP RS

2.7

Varity_R

0.19

gMVP

0.65

Mutation Taster

=98/2

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over