rs952658

Variant names:

• chr12-20712367-G-A
• rs952658
• NM_017435.5:c.529+857G>A

Variant summary

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

The NM_017435.5(SLCO1C1):​c.529+857G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,972 control chromosomes in the GnomAD database, including 7,311 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 0.28 (7311 hom., cov: 32)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 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.529+857G>A		intron	N/A	NP_059131.1
	SLCO1C1	NM_001145946.2		c.529+857G>A		intron	N/A	NP_001139418.1
	SLCO1C1	NM_001145945.2		c.529+857G>A		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.529+857G>A		intron	N/A	ENSP00000266509.2
	SLCO1C1	ENST00000539415.5	TSL:1	n.*113+857G>A		intron	N/A	ENSP00000437399.1
	SLCO1C1	ENST00000545604.5	TSL:2	c.529+857G>A		intron	N/A	ENSP00000444149.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43090 AN: 151852 Hom.: 7279 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.284 AC: 43170 AN: 151972 Hom.: 7311 Cov.: 32 AF XY: 0.276 AC XY: 20528 AN XY: 74314

African (AFR) AF: 0.458 AC: 18964 AN: 41404

American (AMR) AF: 0.237 AC: 3612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.0636 AC: 328 AN: 5156

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4828

European-Finnish (FIN) AF: 0.149 AC: 1580 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15706 AN: 67956

Other (OTH) AF: 0.308 AC: 648 AN: 2106

Alfa AF: 0.255 Hom.: 9997

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.35
PhyloP100		-1.3
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: rs952658; hg19: chr12-20865301; COSMIC: COSV56874391;