rs2417862

Positions:

• chr12-20717331-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.775+101T>C		intron_variant		ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.775+101T>C		intron_variant			NP_001139418.1
SLCO1C1	NM_001145945.2	c.628+101T>C		intron_variant			NP_001139417.1
SLCO1C1	NM_001145944.2	c.421+101T>C		intron_variant			NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.775+101T>C		intron_variant		1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37607 AN: 151838 Hom.: 4910 Cov.: 32

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

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.0572

Gnomad4 SAS exome AF: 0.0985

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.248 AC: 37642 AN: 151954 Hom.: 4911 Cov.: 32 AF XY: 0.241 AC XY: 17880 AN XY: 74278

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.258

Alfa AF: 0.265 Hom.: 10675

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
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2417862; hg19: chr12-20870265;