rs9514091

Variant names:

• chr13-103061904-G-A
• rs9514091
• NM_000452.3:c.378-3522C>T

Variant summary

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

The NM_000452.3(SLC10A2):​c.378-3522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,774 control chromosomes in the GnomAD database, including 5,849 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 0.26 (5849 hom., cov: 33)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 14 publications found

Genes affected

SLC10A2 (HGNC:10906): (solute carrier family 10 member 2) This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

SLC10A2 Gene-Disease associations (from GenCC):

• bile acid malabsorption, primary, 1

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.378-3522C>T		intron_variant	Intron 1 of 5	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.378-3522C>T		intron_variant	Intron 1 of 5	1	NM_000452.3	ENSP00000245312.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38909 AN: 151656 Hom.: 5838 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.257 AC: 38956 AN: 151774 Hom.: 5849 Cov.: 33 AF XY: 0.254 AC XY: 18841 AN XY: 74142

African (AFR) AF: 0.413 AC: 17078 AN: 41366

American (AMR) AF: 0.219 AC: 3344 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.108 AC: 559 AN: 5166

South Asian (SAS) AF: 0.170 AC: 814 AN: 4800

European-Finnish (FIN) AF: 0.174 AC: 1826 AN: 10470

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.198 AC: 13424 AN: 67942

Other (OTH) AF: 0.236 AC: 499 AN: 2112

Alfa AF: 0.233 Hom.: 3242

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.74
PhyloP100		-0.92
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: rs9514091; hg19: chr13-103714254;