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GeneBe

12-20733007-T-C

Variant summary

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

The NM_017435.5(SLCO1C1):c.1285T>C(p.Leu429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,880 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 3 hom. )

Consequence

SLCO1C1
NM_017435.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.364
Variant links:
Genes affected
SLCO1C1 (HGNC:13819): (solute carrier organic anion transporter family member 1C1) This gene encodes a member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of thyroid hormones in brain tissues. This protein has particularly high affinity for the thyroid hormones thyroxine, tri-iodothyronine and reverse tri-iodothyronine. Polymorphisms in the gene encoding this protein may be associated with fatigue and depression in patients suffering from hyperthyroidism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

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=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-20733007-T-C is Benign according to our data. Variant chr12-20733007-T-C is described in ClinVar as [Benign]. Clinvar id is 716429.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=0.364 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 = 0.00609 (927/152268) while in subpopulation AFR AF= 0.0216 (898/41544). AF 95% confidence interval is 0.0204. There are 11 homozygotes in gnomad4. There are 454 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 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1C1NM_017435.5 linkuse as main transcriptc.1285T>C p.Leu429= synonymous_variant 10/15 ENST00000266509.7
SLCO1C1NM_001145946.2 linkuse as main transcriptc.1285T>C p.Leu429= synonymous_variant 11/16
SLCO1C1NM_001145945.2 linkuse as main transcriptc.1138T>C p.Leu380= synonymous_variant 10/15
SLCO1C1NM_001145944.2 linkuse as main transcriptc.931T>C p.Leu311= synonymous_variant 8/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1C1ENST00000266509.7 linkuse as main transcriptc.1285T>C p.Leu429= synonymous_variant 10/151 NM_017435.5 P1Q9NYB5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00598
AC:
910
AN:
152150
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0213
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
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:
0.0000441
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00155
AC:
388
AN:
251036
Hom.:
2
AF XY:
0.00113
AC XY:
153
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.0219
Gnomad AMR exome
AF:
0.000724
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:
0.0000264
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000484
AC:
708
AN:
1461612
Hom.:
3
Cov.:
31
AF XY:
0.000418
AC XY:
304
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.0177
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00609
AC:
927
AN:
152268
Hom.:
11
Cov.:
32
AF XY:
0.00610
AC XY:
454
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0216
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00163
Hom.:
3
Bravo
AF:
0.00666
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
6.2
Dann
Benign
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs74471820; hg19: chr12-20885941; API