rs16961281

Variant names:

• chr13-103066474-G-A
• rs16961281
• NM_000452.3:c.-225C>T

Variant summary

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

The NM_000452.3(SLC10A2):​c.-225C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 459,014 control chromosomes in the GnomAD database, including 1,429 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 0.081 (553 hom., cov: 32)
  • Exomes 𝑓: 0.072 (876 hom.)
• Consequence: SLC10A2 NM_000452.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.-225C>T		upstream_gene_variant		ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.-225C>T		upstream_gene_variant		1	NM_000452.3	ENSP00000245312.3

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12278 AN: 152132 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0720 AC: 22089 AN: 306764 Hom.: 876 Cov.: 4 AF XY: 0.0715 AC XY: 11178 AN XY: 156282

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0571

Gnomad4 SAS exome AF: 0.0581

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0671

Gnomad4 OTH exome AF: 0.0810

GnomAD4 genome AF: 0.0807 AC: 12294 AN: 152250 Hom.: 553 Cov.: 32 AF XY: 0.0818 AC XY: 6087 AN XY: 74428

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0637

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0668 Hom.: 583

Bravo AF: 0.0784

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.2
DANN	Benign	0.67

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: rs16961281; hg19: chr13-103718824;