rs17556915

Variant names:

• chr14-69781641-G-A
• rs17556915
• NM_003049.4:c.568-2281C>T

Variant summary

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

The NM_003049.4(SLC10A1):​c.568-2281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,244 control chromosomes in the GnomAD database, including 1,833 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 0.13 (1833 hom., cov: 32)
• Consequence: SLC10A1 NM_003049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 8 publications found

Genes affected

SLC10A1 (HGNC:10905): (solute carrier family 10 member 1) The protein encoded by this gene belongs to the sodium/bile acid cotransporter family, which are integral membrane glycoproteins that participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids; the ileal sodium/bile acid cotransporter with an apical cell localization that absorbs bile acids from the intestinal lumen, bile duct and kidney, and the liver-specific sodium/bile acid cotransporter, represented by this protein, that is found in the basolateral membranes of hepatocytes. Bile acids are the catabolic product of cholesterol metabolism, hence this protein is important for cholesterol homeostasis. [provided by RefSeq, Oct 2011]

SLC10A1 Gene-Disease associations (from GenCC):

• hypercholanemia, familial, 2

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A1	NM_003049.4	c.568-2281C>T		intron_variant	Intron 2 of 4	ENST00000216540.5	NP_003040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A1	ENST00000216540.5	c.568-2281C>T		intron_variant	Intron 2 of 4	1	NM_003049.4	ENSP00000216540.4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19970 AN: 152126 Hom.: 1833 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.131 AC: 19960 AN: 152244 Hom.: 1833 Cov.: 32 AF XY: 0.124 AC XY: 9239 AN XY: 74438

African (AFR) AF: 0.0363 AC: 1510 AN: 41580

American (AMR) AF: 0.119 AC: 1813 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1139 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13864 AN: 67986

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.170 Hom.: 4025

Bravo AF: 0.130

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-0.080
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: rs17556915; hg19: chr14-70248358;