12-20702827-T-C

Position:

• chr12-20702827-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.271+1368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,536 control chromosomes in the GnomAD database, including 20,609 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 0.50 (20609 hom., cov: 31)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.271+1368T>C		intron_variant		ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.271+1368T>C		intron_variant			NP_001139418.1
SLCO1C1	NM_001145945.2	c.271+1368T>C		intron_variant			NP_001139417.1
SLCO1C1	NM_001145944.2	c.-83-3122T>C		intron_variant			NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.271+1368T>C		intron_variant		1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76066 AN: 151418 Hom.: 20611 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.502 AC: 76087 AN: 151536 Hom.: 20609 Cov.: 31 AF XY: 0.505 AC XY: 37365 AN XY: 74056

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.517

Alfa AF: 0.570 Hom.: 23185

Bravo AF: 0.481

Asia WGS AF: 0.609 AC: 2118 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.46
DANN	Benign	0.66

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: rs10770704; hg19: chr12-20855761;