dbSNP rs4149179: SLC22A8:c.-16G>T (chr11-63014974-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4 link	c.-16G>T	5_prime_UTR_variant	Exon 2 of 11	ENST00000336232.7	NP_004245.2	Q8TCC7-1
SLC22A8	NM_001184732.2 link	c.-4-12G>T	intron_variant	Intron 1 of 10		NP_001171661.1	Q8TCC7-1B2R807
SLC22A8	NM_001184733.2 link	c.-25-264G>T	intron_variant	Intron 1 of 10		NP_001171662.1	Q8TCC7-4
SLC22A8	NM_001184736.2 link	c.-37+755G>T	intron_variant	Intron 1 of 9		NP_001171665.1	Q8TCC7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7 link	c.-16G>T		5_prime_UTR_variant	Exon 2 of 11	1	NM_004254.4	ENSP00000337335.2		Q8TCC7-1

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

GnomAD3 exomes

AF:

0.000820

AC:

157

AN:

191522

Hom.:

AF XY:

0.000778

AC XY:

AN XY:

101554

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 SAS exome

AF:

0.000258

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.000240

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.000160

Gnomad4 FIN exome

AF:

0.00549

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152224

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00689

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000126

Hom.:

291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.2

DANN

Benign

0.80

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

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