Genetic Variant SLCO1C1:c.*528T>C (chr12-20753056-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017435.5(SLCO1C1):c.*528T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,018 control chromosomes in the GnomAD database, including 17,223 homozygotes. 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 0.45 ( 17222 hom., cov: 32)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

SLCO1C1
NM_017435.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258

Publications

9 publications found

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]

SLCO1C1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SLCO1C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5 link	c.*528T>C	3_prime_UTR_variant	Exon 15 of 15	ENST00000266509.7	NP_059131.1	Q9NYB5-1
SLCO1C1	NM_001145946.2 link	c.*577T>C	3_prime_UTR_variant	Exon 16 of 16		NP_001139418.1	Q9NYB5-3
SLCO1C1	NM_001145945.2 link	c.*528T>C	3_prime_UTR_variant	Exon 15 of 15		NP_001139417.1	Q9NYB5-2
SLCO1C1	NM_001145944.2 link	c.*577T>C	3_prime_UTR_variant	Exon 13 of 13		NP_001139416.1	Q9NYB5-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLCO1C1	ENST00000266509.7 link	c.*528T>C	3_prime_UTR_variant	Exon 15 of 15	1	NM_017435.5	ENSP00000266509.2	Q9NYB5-1
SLCO1C1	ENST00000545102.1 link	c.*577T>C	3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000444527.1	Q9NYB5-4
SLCO1C1	ENST00000540354.5 link	c.*528T>C	downstream_gene_variant		2		ENSP00000438665.1	Q9NYB5-2

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69091

AN:

151892

Hom.:

17219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.434

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.455

AC:

69110

AN:

152012

Hom.:

17222

Cov.:

AF XY:

0.458

AC XY:

34016

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.239

AC:

9895

AN:

41480

American (AMR)

AF:

0.548

AC:

8363

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1790

AN:

3470

East Asian (EAS)

AF:

0.598

AC:

3084

AN:

5154

South Asian (SAS)

AF:

0.592

AC:

2855

AN:

4820

European-Finnish (FIN)

AF:

0.484

AC:

5099

AN:

10546

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.535

AC:

36358

AN:

67970

Other (OTH)

AF:

0.433

AC:

914

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1780

3559

5339

7118

8898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.483

Hom.:

17970

Bravo

AF:

0.453

Asia WGS

AF:

0.565

AC:

1961

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.1

(source)

DANN

Benign

0.89

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over