chr12-20712367-G-A

Position:

• chr12-20712367-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1C1	NM_017435.5	c.529+857G>A		intron_variant		ENST00000266509.7	NP_059131.1
SLCO1C1	NM_001145944.2	c.175+857G>A		intron_variant			NP_001139416.1
SLCO1C1	NM_001145945.2	c.529+857G>A		intron_variant			NP_001139417.1
SLCO1C1	NM_001145946.2	c.529+857G>A		intron_variant			NP_001139418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.529+857G>A		intron_variant		1	NM_017435.5	ENSP00000266509	P1

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

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0636

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.308

Alfa AF: 0.250 Hom.: 6867

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.35

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: rs952658; hg19: chr12-20865301; COSMIC: COSV56874391;