rs9514089

Positions:

• chr13-103058487-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000245312.5(SLC10A2):​c.378-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 734,904 control chromosomes in the GnomAD database, including 55,859 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 0.41 (12974 hom., cov: 31)
  • Exomes 𝑓: 0.38 (42885 hom.)
• Consequence: SLC10A2 ENST00000245312.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.378-105A>G		intron_variant		ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.378-105A>G		intron_variant		1	NM_000452.3	ENSP00000245312	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61982 AN: 151898 Hom.: 12953 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.378 AC: 220118 AN: 582888 Hom.: 42885 AF XY: 0.380 AC XY: 119219 AN XY: 313912

Gnomad4 AFR exome AF: 0.493

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.408 AC: 62044 AN: 152016 Hom.: 12974 Cov.: 31 AF XY: 0.408 AC XY: 30310 AN XY: 74318

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.422

Alfa AF: 0.399 Hom.: 1537

Bravo AF: 0.406

Asia WGS AF: 0.376 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.58

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: rs9514089; hg19: chr13-103710837;