Menu
GeneBe

6-160132274-C-T

Variant summary

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

The NM_003057.3(SLC22A1):c.558C>T(p.Asn186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,606,536 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 11 hom. )

Consequence

SLC22A1
NM_003057.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.10
Variant links:
Genes affected
SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

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=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-160132274-C-T is Benign according to our data. Variant chr6-160132274-C-T is described in ClinVar as [Benign]. Clinvar id is 789005.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=-4.1 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 = 0.00813 (1239/152348) while in subpopulation AFR AF= 0.0282 (1171/41574). AF 95% confidence interval is 0.0268. There are 19 homozygotes in gnomad4. There are 591 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 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A1NM_003057.3 linkuse as main transcriptc.558C>T p.Asn186= synonymous_variant 3/11 ENST00000366963.9
SLC22A1NM_153187.2 linkuse as main transcriptc.558C>T p.Asn186= synonymous_variant 3/10
SLC22A1XM_005267103.3 linkuse as main transcriptc.558C>T p.Asn186= synonymous_variant 3/12
SLC22A1XM_006715552.3 linkuse as main transcriptc.558C>T p.Asn186= synonymous_variant 3/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A1ENST00000366963.9 linkuse as main transcriptc.558C>T p.Asn186= synonymous_variant 3/111 NM_003057.3 P1O15245-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00813
AC:
1238
AN:
152230
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0282
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00219
AC:
534
AN:
244272
Hom.:
9
AF XY:
0.00165
AC XY:
218
AN XY:
131898
show subpopulations
Gnomad AFR exome
AF:
0.0290
Gnomad AMR exome
AF:
0.000834
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000346
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000224
Gnomad OTH exome
AF:
0.00120
GnomAD4 exome
AF:
0.000959
AC:
1395
AN:
1454188
Hom.:
11
Cov.:
31
AF XY:
0.000830
AC XY:
600
AN XY:
723066
show subpopulations
Gnomad4 AFR exome
AF:
0.0298
Gnomad4 AMR exome
AF:
0.000941
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000284
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000168
Gnomad4 OTH exome
AF:
0.00233
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00813
AC:
1239
AN:
152348
Hom.:
19
Cov.:
32
AF XY:
0.00793
AC XY:
591
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.0282
Gnomad4 AMR
AF:
0.00248
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00252
Hom.:
9
Bravo
AF:
0.00920
Asia WGS
AF:
0.00318
AC:
12
AN:
3478

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 testingInvitaeJun 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.040
Dann
Benign
0.61

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: rs34134157; hg19: chr6-160553306; COSMIC: COSV61452240; API