Genetic Variant SLC22A8:c.-16G>T (chr11-63014974-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004254.4(SLC22A8):c.-16G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,530,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

SLC22A8
NM_004254.4 5_prime_UTR

Scores

Splicing: ADA: 0.00002447

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.22

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC22A8	NM_004254.4	MANE Select	c.-16G>T	5_prime_UTR	Exon 2 of 11	NP_004245.2
SLC22A8	NM_001184732.2		c.-4-12G>T	intron	N/A	NP_001171661.1	Q8TCC7-1
SLC22A8	NM_001184733.2		c.-25-264G>T	intron	N/A	NP_001171662.1	Q8TCC7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.-16G>T	5_prime_UTR	Exon 2 of 11	ENSP00000337335.2	Q8TCC7-1
SLC22A8	ENST00000430500.6	TSL:1	c.-4-12G>T	intron	N/A	ENSP00000398548.2	Q8TCC7-1
SLC22A8	ENST00000535878.5	TSL:1	c.-37+755G>T	intron	N/A	ENSP00000443368.1	Q8TCC7-5

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00689

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000820

AC:

157

AN:

191522

AF XY:

0.000778

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.0000392

Gnomad ASJ exome

AF:

0.000231

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00579

Gnomad NFE exome

AF:

0.000509

Gnomad OTH exome

AF:

0.000909

GnomAD4 exome

AF:

0.000376

AC:

519

AN:

1378684

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

245

AN XY:

675484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31076

American (AMR)

AF:

0.0000289

AC:

AN:

34652

Ashkenazi Jewish (ASJ)

AF:

0.000240

AC:

AN:

20830

East Asian (EAS)

AF:

0.0000516

AC:

AN:

38744

South Asian (SAS)

AF:

0.000160

AC:

AN:

74908

European-Finnish (FIN)

AF:

0.00549

AC:

275

AN:

50074

Middle Eastern (MID)

AF:

0.00168

AC:

AN:

5342

European-Non Finnish (NFE)

AF:

0.000171

AC:

182

AN:

1066462

Other (OTH)

AF:

0.000583

AC:

AN:

56596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152224

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00689

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000780

Hom.:

552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.2

(source)

DANN

Benign

0.80

PhyloP100

-4.2

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: -12

DS_AL_spliceai

0.31

Position offset: 9

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

Computational scores

Splicing

Publications

Other links and lift over