Genetic Variant SLC22A8:c.437+79G>A (chr11-63000641-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004254.4(SLC22A8):c.437+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,020,398 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SLC22A8
NM_004254.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

15 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.437+79G>A	intron	N/A	NP_004245.2
SLC22A8	NM_001184732.2		c.437+79G>A	intron	N/A	NP_001171661.1	Q8TCC7-1
SLC22A8	NM_001184733.2		c.164+79G>A	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.437+79G>A	intron	N/A	ENSP00000337335.2	Q8TCC7-1
SLC22A8	ENST00000430500.6	TSL:1	c.437+79G>A	intron	N/A	ENSP00000398548.2	Q8TCC7-1
SLC22A8	ENST00000311438.12	TSL:1	c.437+79G>A	intron	N/A	ENSP00000311463.8	H7BXN9

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

868514

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

449912

show subpopulations

African (AFR)

AF:

0.0000457

AC:

AN:

21904

American (AMR)

AF:

0.0000509

AC:

AN:

39302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20876

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35270

South Asian (SAS)

AF:

0.0000436

AC:

AN:

68772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4558

European-Non Finnish (NFE)

AF:

0.00000846

AC:

AN:

590716

Other (OTH)

AF:

0.0000246

AC:

AN:

40620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

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:

0.0000198

AC:

AN:

151884

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41298

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00

Hom.:

272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.91

PhyloP100

-1.1

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over