12-20740175-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017435.5(SLCO1C1):c.1549-9G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,598,082 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (43 hom.)
• Consequence: SLCO1C1 NM_017435.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001958
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-20740175-G-T is Benign according to our data. Variant chr12-20740175-G-T is described in ClinVar as [Benign]. Clinvar id is 710132.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-20740175-G-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2179/152070) while in subpopulation AFR AF= 0.0475 (1971/41468). AF 95% confidence interval is 0.0458. There are 55 homozygotes in gnomad4. There are 982 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1C1	NM_017435.5	c.1549-9G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000266509.7
SLCO1C1	NM_001145944.2	c.1195-9G>T		splice_polypyrimidine_tract_variant, intron_variant
SLCO1C1	NM_001145945.2	c.1402-9G>T		splice_polypyrimidine_tract_variant, intron_variant
SLCO1C1	NM_001145946.2	c.1549-9G>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1C1	ENST00000266509.7	c.1549-9G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017435.5	P1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2180 AN: 151952 Hom.: 55 Cov.: 31

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00833

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00407 AC: 967 AN: 237472 Hom.: 26 AF XY: 0.00299 AC XY: 385 AN XY: 128668

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00479

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000394

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000530

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00173 AC: 2502 AN: 1446012 Hom.: 43 Cov.: 33 AF XY: 0.00156 AC XY: 1119 AN XY: 719150

Gnomad4 AFR exome AF: 0.0481

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.00394

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000408

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000363

Gnomad4 OTH exome AF: 0.00330

GnomAD4 genome AF: 0.0143 AC: 2179 AN: 152070 Hom.: 55 Cov.: 31 AF XY: 0.0132 AC XY: 982 AN XY: 74328

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00832

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00622 Hom.: 15

Bravo AF: 0.0164

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.0
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs12304500; hg19: chr12-20893109;