rs2301159

Positions:

• chr13-103045378-G-A

Variant summary

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

The NM_000452.3(SLC10A2):​c.*755C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,058 control chromosomes in the GnomAD database, including 5,758 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 0.27 (5756 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: SLC10A2 NM_000452.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.*755C>T		3_prime_UTR_variant	6/6	ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.*755C>T		3_prime_UTR_variant	6/6	1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40752 AN: 151864 Hom.: 5751 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.158 AC: 12 AN: 76 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 10 AN XY: 60

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.118

GnomAD4 genome AF: 0.268 AC: 40796 AN: 151982 Hom.: 5756 Cov.: 32 AF XY: 0.266 AC XY: 19748 AN XY: 74272

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.279

Alfa AF: 0.248 Hom.: 9407

Bravo AF: 0.276

Asia WGS AF: 0.273 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
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: rs2301159; hg19: chr13-103697728;