Genetic Variant NM_004254.4:c.-16G>A (chr11-63014974-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004254.4(SLC22A8):c.-16G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,530,816 control chromosomes in the GnomAD database, including 2,777 homozygotes. 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 0.053 ( 420 hom., cov: 33)

Exomes 𝑓: 0.041 ( 2357 hom. )

Consequence

SLC22A8
NM_004254.4 5_prime_UTR

Scores

Splicing: ADA: 0.00009464

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4 link	c.-16G>A	5_prime_UTR_variant	Exon 2 of 11	ENST00000336232.7	NP_004245.2	Q8TCC7-1
SLC22A8	NM_001184732.2 link	c.-4-12G>A	intron_variant	Intron 1 of 10		NP_001171661.1	Q8TCC7-1B2R807
SLC22A8	NM_001184733.2 link	c.-25-264G>A	intron_variant	Intron 1 of 10		NP_001171662.1	Q8TCC7-4
SLC22A8	NM_001184736.2 link	c.-37+755G>A	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>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_004254.4	ENSP00000337335.2		Q8TCC7-1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8104

AN:

152096

Hom.:

422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0511

GnomAD2 exomes

AF:

0.0765

AC:

14660

AN:

191522

AF XY:

0.0703

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0240

Gnomad EAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.0455

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0411

AC:

56626

AN:

1378602

Hom.:

2357

Cov.:

AF XY:

0.0407

AC XY:

27461

AN XY:

675438

show subpopulations

African (AFR)

AF:

0.0556

AC:

1728

AN:

31076

American (AMR)

AF:

0.161

AC:

5577

AN:

34638

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

419

AN:

20830

East Asian (EAS)

AF:

0.238

AC:

9225

AN:

38742

South Asian (SAS)

AF:

0.0499

AC:

3740

AN:

74900

European-Finnish (FIN)

AF:

0.0418

AC:

2095

AN:

50074

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

5340

European-Non Finnish (NFE)

AF:

0.0292

AC:

31146

AN:

1066410

Other (OTH)

AF:

0.0459

AC:

2597

AN:

56592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2919

5838

8756

11675

14594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1422

2844

4266

5688

7110

<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:

0.0532

AC:

8104

AN:

152214

Hom.:

420

Cov.:

AF XY:

0.0547

AC XY:

4067

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0560

AC:

2327

AN:

41536

American (AMR)

AF:

0.103

AC:

1581

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3470

East Asian (EAS)

AF:

0.246

AC:

1268

AN:

5164

South Asian (SAS)

AF:

0.0532

AC:

256

AN:

4814

European-Finnish (FIN)

AF:

0.0388

AC:

411

AN:

10596

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0306

AC:

2080

AN:

68010

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

382

765

1147

1530

1912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0380

Hom.:

552

Bravo

AF:

0.0602

Asia WGS

AF:

0.154

AC:

533

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.6

(source)

DANN

Benign

0.82

PhyloP100

-4.2

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000095

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

Other links and lift over