dbSNP rs200993713: SLCO1C1:c.272-8C>T (chr12-20705941-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017435.5(SLCO1C1):c.272-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,611,800 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 6 hom. )

Consequence

SLCO1C1
NM_017435.5 splice_region, intron

Scores

Splicing: ADA: 0.0001951

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0630

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 12-20705941-C-T is Benign according to our data. Variant chr12-20705941-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3777823.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017435.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLCO1C1	NM_017435.5	MANE Select	c.272-8C>T	splice_region intron	N/A	NP_059131.1	Q9NYB5-1
SLCO1C1	NM_001145946.2		c.272-8C>T	splice_region intron	N/A	NP_001139418.1	Q9NYB5-3
SLCO1C1	NM_001145945.2		c.272-8C>T	splice_region intron	N/A	NP_001139417.1	Q9NYB5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLCO1C1	ENST00000266509.7	TSL:1 MANE Select	c.272-8C>T	splice_region intron	N/A	ENSP00000266509.2	Q9NYB5-1
SLCO1C1	ENST00000539415.5	TSL:1	n.130-5445C>T	intron	N/A	ENSP00000437399.1	F5H6S4
SLCO1C1	ENST00000545604.5	TSL:2	c.272-8C>T	splice_region intron	N/A	ENSP00000444149.1	Q9NYB5-3

Frequencies

GnomAD3 genomes

AF:

0.000645

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000592

AC:

148

AN:

249814

AF XY:

0.000607

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000601

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000404

AC:

590

AN:

1459706

Hom.:

Cov.:

AF XY:

0.000405

AC XY:

294

AN XY:

726148

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33372

American (AMR)

AF:

0.00159

AC:

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.000279

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.0117

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000293

AC:

325

AN:

1110750

Other (OTH)

AF:

0.00111

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000644

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41520

American (AMR)

AF:

0.00282

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000530

AC:

AN:

67918

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00137

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.6

(source)

DANN

Benign

0.57

PhyloP100

0.063

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.014

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over