NM_017435.5:c.404+1078G>A

Variant names:

• chr12-20707159-G-A
• rs3794271
• NM_017435.5:c.404+1078G>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.404+1078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,776 control chromosomes in the GnomAD database, including 24,472 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 0.56 (24472 hom., cov: 31)
• Consequence: SLCO1C1 NM_017435.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 35 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 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.404+1078G>A		intron	N/A	NP_059131.1	Q9NYB5-1
	SLCO1C1	NM_001145946.2		c.404+1078G>A		intron	N/A	NP_001139418.1	Q9NYB5-3
	SLCO1C1	NM_001145945.2		c.404+1078G>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.404+1078G>A		intron	N/A	ENSP00000266509.2	Q9NYB5-1
	SLCO1C1	ENST00000539415.5	TSL:1	n.130-4227G>A		intron	N/A	ENSP00000437399.1	F5H6S4
	SLCO1C1	ENST00000545604.5	TSL:2	c.404+1078G>A		intron	N/A	ENSP00000444149.1	Q9NYB5-3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84805 AN: 151658 Hom.: 24466 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.559 AC: 84841 AN: 151776 Hom.: 24472 Cov.: 31 AF XY: 0.560 AC XY: 41534 AN XY: 74142

African (AFR) AF: 0.429 AC: 17753 AN: 41344

American (AMR) AF: 0.469 AC: 7159 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2572 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3809 AN: 5114

South Asian (SAS) AF: 0.680 AC: 3274 AN: 4816

European-Finnish (FIN) AF: 0.627 AC: 6601 AN: 10532

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41671 AN: 67936

Other (OTH) AF: 0.577 AC: 1214 AN: 2104

Alfa AF: 0.599 Hom.: 122641

Bravo AF: 0.543

Asia WGS AF: 0.650 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.25
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: rs3794271; hg19: chr12-20860093;