chr12-20717331-T-C

Variant names:

• chr12-20717331-T-C
• rs2417862
• NM_017435.5:c.775+101T>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.775+101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 868,622 control chromosomes in the GnomAD database, including 28,739 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 0.25 (4911 hom., cov: 32)
  • Exomes 𝑓: 0.24 (23828 hom.)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.775+101T>C		intron_variant	Intron 7 of 14	ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145946.2	c.775+101T>C		intron_variant	Intron 8 of 15		NP_001139418.1
SLCO1C1	NM_001145945.2	c.628+101T>C		intron_variant	Intron 7 of 14		NP_001139417.1
SLCO1C1	NM_001145944.2	c.421+101T>C		intron_variant	Intron 5 of 12		NP_001139416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.775+101T>C		intron_variant	Intron 7 of 14	1	NM_017435.5	ENSP00000266509.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37607 AN: 151838 Hom.: 4910 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.245 AC: 175328 AN: 716668 Hom.: 23828 AF XY: 0.240 AC XY: 89537 AN XY: 373388

African (AFR) AF: 0.262 AC: 3604 AN: 13770

American (AMR) AF: 0.207 AC: 3065 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 4208 AN: 17224

East Asian (EAS) AF: 0.0572 AC: 1589 AN: 27772

South Asian (SAS) AF: 0.0985 AC: 4945 AN: 50192

European-Finnish (FIN) AF: 0.247 AC: 10192 AN: 41344

Middle Eastern (MID) AF: 0.216 AC: 638 AN: 2952

European-Non Finnish (NFE) AF: 0.270 AC: 138937 AN: 514792

Other (OTH) AF: 0.241 AC: 8150 AN: 33826

GnomAD4 genome AF: 0.248 AC: 37642 AN: 151954 Hom.: 4911 Cov.: 32 AF XY: 0.241 AC XY: 17880 AN XY: 74278

African (AFR) AF: 0.260 AC: 10763 AN: 41472

American (AMR) AF: 0.229 AC: 3494 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 886 AN: 3464

East Asian (EAS) AF: 0.0391 AC: 203 AN: 5188

South Asian (SAS) AF: 0.0981 AC: 473 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2649 AN: 10492

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18426 AN: 67936

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.264 Hom.: 20081

Bravo AF: 0.250

Asia WGS AF: 0.106 AC: 371 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.71
PhyloP100		-3.2
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: rs2417862; hg19: chr12-20870265;