Menu
GeneBe

rs12777

chr5-132335969-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003059.3(SLC22A4):c.1413C>G(p.Gly471=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,614,026 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 79 hom., cov: 32)
Exomes 𝑓: 0.037 ( 1193 hom. )

Consequence

SLC22A4
NM_003059.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.311
Variant links:
Genes affected
SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]
MIR3936HG (HGNC:40538): (MIR3936 host gene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-132335969-C-G is Benign according to our data. Variant chr5-132335969-C-G is described in ClinVar as [Benign]. Clinvar id is 805281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=0.311 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A4NM_003059.3 linkuse as main transcriptc.1413C>G p.Gly471= synonymous_variant 8/10 ENST00000200652.4
MIR3936HGNR_110997.1 linkuse as main transcriptn.561-1043G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A4ENST00000200652.4 linkuse as main transcriptc.1413C>G p.Gly471= synonymous_variant 8/101 NM_003059.3 P1
MIR3936HGENST00000621103.4 linkuse as main transcriptn.561-1043G>C intron_variant, non_coding_transcript_variant 1
MIR3936HGENST00000616965.1 linkuse as main transcriptn.344-1043G>C intron_variant, non_coding_transcript_variant 5
MIR3936HGENST00000669845.1 linkuse as main transcriptn.187-1043G>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0280
AC:
4258
AN:
152184
Hom.:
79
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00734
Gnomad AMI
AF:
0.0461
Gnomad AMR
AF:
0.0325
Gnomad ASJ
AF:
0.0703
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0145
Gnomad FIN
AF:
0.0246
Gnomad MID
AF:
0.146
Gnomad NFE
AF:
0.0399
Gnomad OTH
AF:
0.0388
GnomAD3 exomes
AF:
0.0305
AC:
7672
AN:
251390
Hom.:
170
AF XY:
0.0312
AC XY:
4233
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00677
Gnomad AMR exome
AF:
0.0269
Gnomad ASJ exome
AF:
0.0652
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.0144
Gnomad FIN exome
AF:
0.0246
Gnomad NFE exome
AF:
0.0414
Gnomad OTH exome
AF:
0.0478
GnomAD4 exome
AF:
0.0372
AC:
54351
AN:
1461724
Hom.:
1193
Cov.:
32
AF XY:
0.0372
AC XY:
27043
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00965
Gnomad4 AMR exome
AF:
0.0270
Gnomad4 ASJ exome
AF:
0.0614
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0160
Gnomad4 FIN exome
AF:
0.0248
Gnomad4 NFE exome
AF:
0.0409
Gnomad4 OTH exome
AF:
0.0379
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0279
AC:
4256
AN:
152302
Hom.:
79
Cov.:
32
AF XY:
0.0275
AC XY:
2046
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00729
Gnomad4 AMR
AF:
0.0325
Gnomad4 ASJ
AF:
0.0703
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0145
Gnomad4 FIN
AF:
0.0246
Gnomad4 NFE
AF:
0.0399
Gnomad4 OTH
AF:
0.0384
Alfa
AF:
0.0408
Hom.:
119
Bravo
AF:
0.0276
Asia WGS
AF:
0.0110
AC:
37
AN:
3478
EpiCase
AF:
0.0467
EpiControl
AF:
0.0461

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsFeb 27, 2019- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
8.9
Dann
Benign
0.70

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: rs12777; hg19: chr5-131671662; API