chr12-20753056-T-C

Position:

• chr12-20753056-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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1C1	NM_017435.5	c.*528T>C		3_prime_UTR_variant	15/15	ENST00000266509.7
SLCO1C1	NM_001145944.2	c.*577T>C		3_prime_UTR_variant	13/13
SLCO1C1	NM_001145945.2	c.*528T>C		3_prime_UTR_variant	15/15
SLCO1C1	NM_001145946.2	c.*577T>C		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.*528T>C		3_prime_UTR_variant	15/15	1	NM_017435.5	P1
SLCO1C1	ENST00000545102.1	c.*577T>C		3_prime_UTR_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69091 AN: 151892 Hom.: 17219 Cov.: 32

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: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.455 AC: 69110 AN: 152012 Hom.: 17222 Cov.: 32 AF XY: 0.458 AC XY: 34016 AN XY: 74300

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.433

Alfa AF: 0.502 Hom.: 8366

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
DANN	Benign	0.89

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: rs10444412; hg19: chr12-20905990;