chr13-103066474-G-A

Variant names:

• chr13-103066474-G-A
• rs16961281
• NM_000452.3:c.-225C>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.-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
• Publications: 8 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.-225C>T		upstream_gene	N/A	NP_000443.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.-225C>T		upstream_gene	N/A	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

African (AFR) AF: 0.121 AC: 1221 AN: 10112

American (AMR) AF: 0.0490 AC: 550 AN: 11226

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 1235 AN: 10462

East Asian (EAS) AF: 0.0571 AC: 1493 AN: 26164

South Asian (SAS) AF: 0.0581 AC: 672 AN: 11560

European-Finnish (FIN) AF: 0.101 AC: 2157 AN: 21356

Middle Eastern (MID) AF: 0.0735 AC: 112 AN: 1524

European-Non Finnish (NFE) AF: 0.0671 AC: 13070 AN: 194870

Other (OTH) AF: 0.0810 AC: 1579 AN: 19490

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

African (AFR) AF: 0.114 AC: 4737 AN: 41544

American (AMR) AF: 0.0569 AC: 871 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3466

East Asian (EAS) AF: 0.0637 AC: 330 AN: 5180

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4826

European-Finnish (FIN) AF: 0.106 AC: 1117 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4393 AN: 68026

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0683 Hom.: 746

Bravo AF: 0.0784

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.2
DANN	Benign	0.67
PhyloP100		0.97
PromoterAI		-0.0038	Neutral
Mutation Taster		=300/0	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: rs16961281; hg19: chr13-103718824;