chr12-20704533-A-C

Variant names:

• chr12-20704533-A-C
• rs10770705
• NM_017435.5:c.272-1416A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017435.5(SLCO1C1):​c.272-1416A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,166 control chromosomes in the GnomAD database, including 37,600 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 0.70 (37600 hom., cov: 31)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 45 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017435.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	NM_017435.5	MANE Select	c.272-1416A>C		intron	N/A	NP_059131.1
	SLCO1C1	NM_001145946.2		c.272-1416A>C		intron	N/A	NP_001139418.1
	SLCO1C1	NM_001145945.2		c.272-1416A>C		intron	N/A	NP_001139417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	ENST00000266509.7	TSL:1 MANE Select	c.272-1416A>C		intron	N/A	ENSP00000266509.2
	SLCO1C1	ENST00000539415.5	TSL:1	n.129+4828A>C		intron	N/A	ENSP00000437399.1
	SLCO1C1	ENST00000545604.5	TSL:2	c.272-1416A>C		intron	N/A	ENSP00000444149.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106099 AN: 151050 Hom.: 37565 Cov.: 31

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.719

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.702 AC: 106189 AN: 151166 Hom.: 37600 Cov.: 31 AF XY: 0.702 AC XY: 51838 AN XY: 73876

African (AFR) AF: 0.758 AC: 31310 AN: 41292

American (AMR) AF: 0.571 AC: 8674 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2759 AN: 3444

East Asian (EAS) AF: 0.814 AC: 4167 AN: 5120

South Asian (SAS) AF: 0.749 AC: 3602 AN: 4812

European-Finnish (FIN) AF: 0.700 AC: 7353 AN: 10502

Middle Eastern (MID) AF: 0.729 AC: 210 AN: 288

European-Non Finnish (NFE) AF: 0.681 AC: 45954 AN: 67522

Other (OTH) AF: 0.702 AC: 1472 AN: 2098

Alfa AF: 0.689 Hom.: 120478

Bravo AF: 0.694

Asia WGS AF: 0.743 AC: 2584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.40
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10770705; hg19: chr12-20857467;