chr13-103045818-A-C

Variant names:

• chr13-103045818-A-C
• rs279941
• NM_000452.3:c.*315T>G

Variant summary

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

The NM_000452.3(SLC10A2):​c.*315T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 210,524 control chromosomes in the GnomAD database, including 81,136 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 0.88 (59000 hom., cov: 29)
  • Exomes 𝑓: 0.87 (22136 hom.)
• Consequence: SLC10A2 NM_000452.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 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.*315T>G		3_prime_UTR	Exon 6 of 6	NP_000443.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.*315T>G		3_prime_UTR	Exon 6 of 6	ENSP00000245312.3

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133587 AN: 151788 Hom.: 58949 Cov.: 29

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.866 AC: 50782 AN: 58618 Hom.: 22136 Cov.: 2 AF XY: 0.866 AC XY: 26943 AN XY: 31106

African (AFR) AF: 0.921 AC: 1485 AN: 1612

American (AMR) AF: 0.781 AC: 2824 AN: 3618

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 1455 AN: 1680

East Asian (EAS) AF: 0.734 AC: 2474 AN: 3372

South Asian (SAS) AF: 0.858 AC: 5851 AN: 6822

European-Finnish (FIN) AF: 0.883 AC: 2000 AN: 2266

Middle Eastern (MID) AF: 0.920 AC: 195 AN: 212

European-Non Finnish (NFE) AF: 0.883 AC: 31705 AN: 35894

Other (OTH) AF: 0.889 AC: 2793 AN: 3142

GnomAD4 genome AF: 0.880 AC: 133691 AN: 151906 Hom.: 59000 Cov.: 29 AF XY: 0.877 AC XY: 65104 AN XY: 74232

African (AFR) AF: 0.926 AC: 38358 AN: 41402

American (AMR) AF: 0.808 AC: 12314 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3468

East Asian (EAS) AF: 0.740 AC: 3815 AN: 5156

South Asian (SAS) AF: 0.849 AC: 4076 AN: 4802

European-Finnish (FIN) AF: 0.880 AC: 9298 AN: 10564

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.881 AC: 59860 AN: 67968

Other (OTH) AF: 0.869 AC: 1824 AN: 2100

Alfa AF: 0.877 Hom.: 176900

Bravo AF: 0.876

Asia WGS AF: 0.815 AC: 2824 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.045
DANN	Benign	0.48
PhyloP100		-2.5
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: rs279941; hg19: chr13-103698168;