Menu
GeneBe

11-62993276-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004254.4(SLC22A8):c.1590C>A(p.Ile530=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,613,362 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 18 hom., cov: 32)
Exomes 𝑓: 0.00075 ( 24 hom. )

Consequence

SLC22A8
NM_004254.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0660
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-62993276-G-T is Benign according to our data. Variant chr11-62993276-G-T is described in ClinVar as [Benign]. Clinvar id is 710002.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.066 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00783 (1192/152256) while in subpopulation AFR AF= 0.0275 (1141/41544). AF 95% confidence interval is 0.0261. There are 18 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A8NM_004254.4 linkuse as main transcriptc.1590C>A p.Ile530= synonymous_variant 11/11 ENST00000336232.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A8ENST00000336232.7 linkuse as main transcriptc.1590C>A p.Ile530= synonymous_variant 11/111 NM_004254.4 P1Q8TCC7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00782
AC:
1189
AN:
152138
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0275
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
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:
0.0000294
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00199
AC:
499
AN:
250772
Hom.:
7
AF XY:
0.00142
AC XY:
193
AN XY:
135558
show subpopulations
Gnomad AFR exome
AF:
0.0280
Gnomad AMR exome
AF:
0.00125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000750
AC:
1096
AN:
1461106
Hom.:
24
Cov.:
31
AF XY:
0.000630
AC XY:
458
AN XY:
726824
show subpopulations
Gnomad4 AFR exome
AF:
0.0281
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.00116
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00783
AC:
1192
AN:
152256
Hom.:
18
Cov.:
32
AF XY:
0.00762
AC XY:
567
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0275
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.00238
Hom.:
4
Bravo
AF:
0.00859
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
6.4
Dann
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs11568487; hg19: chr11-62760748; API