dbSNP rs2417862: SLCO1C1:c.775+101T>C (chr12-20717331-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.775+101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 868,622 control chromosomes in the GnomAD database, including 28,739 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 0.25 ( 4911 hom., cov: 32)

Exomes 𝑓: 0.24 ( 23828 hom. )

Consequence

SLCO1C1
NM_017435.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.15

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5 link	c.775+101T>C	intron_variant	Intron 7 of 14	ENST00000266509.7	NP_059131.1	Q9NYB5-1
SLCO1C1	NM_001145946.2 link	c.775+101T>C	intron_variant	Intron 8 of 15		NP_001139418.1	Q9NYB5-3
SLCO1C1	NM_001145945.2 link	c.628+101T>C	intron_variant	Intron 7 of 14		NP_001139417.1	Q9NYB5-2
SLCO1C1	NM_001145944.2 link	c.421+101T>C	intron_variant	Intron 5 of 12		NP_001139416.1	Q9NYB5-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7 link	c.775+101T>C		intron_variant	Intron 7 of 14	1	NM_017435.5	ENSP00000266509.2		Q9NYB5-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37607

AN:

151838

Hom.:

4910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.0390

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.245

AC:

175328

AN:

716668

Hom.:

23828

AF XY:

0.240

AC XY:

89537

AN XY:

373388

show subpopulations

African (AFR)

AF:

0.262

AC:

3604

AN:

13770

American (AMR)

AF:

0.207

AC:

3065

AN:

14796

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

4208

AN:

17224

East Asian (EAS)

AF:

0.0572

AC:

1589

AN:

27772

South Asian (SAS)

AF:

0.0985

AC:

4945

AN:

50192

European-Finnish (FIN)

AF:

0.247

AC:

10192

AN:

41344

Middle Eastern (MID)

AF:

0.216

AC:

638

AN:

2952

European-Non Finnish (NFE)

AF:

0.270

AC:

138937

AN:

514792

Other (OTH)

AF:

0.241

AC:

8150

AN:

33826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6181

12363

18544

24726

30907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3198

6396

9594

12792

15990

<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:

0.248

AC:

37642

AN:

151954

Hom.:

4911

Cov.:

AF XY:

0.241

AC XY:

17880

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.260

AC:

10763

AN:

41472

American (AMR)

AF:

0.229

AC:

3494

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

886

AN:

3464

East Asian (EAS)

AF:

0.0391

AC:

203

AN:

5188

South Asian (SAS)

AF:

0.0981

AC:

473

AN:

4824

European-Finnish (FIN)

AF:

0.252

AC:

2649

AN:

10492

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18426

AN:

67936

Other (OTH)

AF:

0.258

AC:

543

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1439

2879

4318

5758

7197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.264

Hom.:

20081

Bravo

AF:

0.250

Asia WGS

AF:

0.106

AC:

371

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.43

(source)

DANN

Benign

0.71

PhyloP100

-3.2

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