Genetic Variant NM_017435.5:c.272-8C>T (chr12-20705941-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5 link	c.272-8C>T	splice_region_variant, intron_variant	Intron 3 of 14	ENST00000266509.7	NP_059131.1	Q9NYB5-1
SLCO1C1	NM_001145946.2 link	c.272-8C>T	splice_region_variant, intron_variant	Intron 4 of 15		NP_001139418.1	Q9NYB5-3
SLCO1C1	NM_001145945.2 link	c.272-8C>T	splice_region_variant, intron_variant	Intron 4 of 14		NP_001139417.1	Q9NYB5-2
SLCO1C1	NM_001145944.2 link	c.-83-8C>T	splice_region_variant, intron_variant	Intron 1 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.272-8C>T		splice_region_variant, intron_variant	Intron 3 of 14	1	NM_017435.5	ENSP00000266509.2		Q9NYB5-1

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

GnomAD3 exomes

AF:

0.000592

AC:

148

AN:

249814

Hom.:

AF XY:

0.000607

AC XY:

AN XY:

135084

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 SAS exome

AF:

0.000296

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

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000644

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00282

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.00237

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.6

DANN

Benign

0.57

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over