rs972505

Variant names:

• chr12-20750301-C-A
• rs972505
• NM_017435.5:c.1799-374C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-20750301-C-A
• chr12-20750301-C-G
• chr12-20750301-C-T

Variant summary

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

The NM_017435.5(SLCO1C1):​c.1799-374C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,808 control chromosomes in the GnomAD database, including 17,775 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 0.46 (17775 hom., cov: 32)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	NM_017435.5	MANE Select	c.1799-374C>A		intron	N/A	NP_059131.1	Q9NYB5-1
	SLCO1C1	NM_001145946.2		c.1799-374C>A		intron	N/A	NP_001139418.1	Q9NYB5-3
	SLCO1C1	NM_001145945.2		c.1652-374C>A		intron	N/A	NP_001139417.1	Q9NYB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1C1	ENST00000266509.7	TSL:1 MANE Select	c.1799-374C>A		intron	N/A	ENSP00000266509.2	Q9NYB5-1
	SLCO1C1	ENST00000539415.5	TSL:1	n.*1383-374C>A		intron	N/A	ENSP00000437399.1	F5H6S4
	SLCO1C1	ENST00000545604.5	TSL:2	c.1799-374C>A		intron	N/A	ENSP00000444149.1	Q9NYB5-3

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69534 AN: 151690 Hom.: 17773 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.458 AC: 69547 AN: 151808 Hom.: 17775 Cov.: 32 AF XY: 0.462 AC XY: 34237 AN XY: 74182

African (AFR) AF: 0.219 AC: 9051 AN: 41376

American (AMR) AF: 0.555 AC: 8482 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3091 AN: 5156

South Asian (SAS) AF: 0.627 AC: 3024 AN: 4822

European-Finnish (FIN) AF: 0.484 AC: 5080 AN: 10504

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37201 AN: 67904

Other (OTH) AF: 0.448 AC: 941 AN: 2102

Alfa AF: 0.515 Hom.: 60142

Bravo AF: 0.456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.020
DANN	Benign	0.37
PhyloP100		-2.4
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: rs972505; hg19: chr12-20903235;