13-103060149-A-G

Variant names:

• chr13-103060149-A-G
• rs157266
• NM_000452.3:c.378-1767T>C

Variant summary

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

The NM_000452.3(SLC10A2):​c.378-1767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,128 control chromosomes in the GnomAD database, including 58,915 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 (58915 hom., cov: 30)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 5 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.378-1767T>C		intron	N/A	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.378-1767T>C		intron	N/A	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133737 AN: 152010 Hom.: 58871 Cov.: 30

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.870

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.880 AC: 133833 AN: 152128 Hom.: 58915 Cov.: 30 AF XY: 0.878 AC XY: 65255 AN XY: 74364

African (AFR) AF: 0.896 AC: 37180 AN: 41480

American (AMR) AF: 0.850 AC: 12996 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3013 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4221 AN: 5148

South Asian (SAS) AF: 0.850 AC: 4099 AN: 4820

European-Finnish (FIN) AF: 0.878 AC: 9310 AN: 10608

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60044 AN: 68002

Other (OTH) AF: 0.872 AC: 1837 AN: 2106

Alfa AF: 0.882 Hom.: 101865

Bravo AF: 0.878

Asia WGS AF: 0.838 AC: 2915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.98
DANN	Benign	0.38
PhyloP100		-0.26
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: rs157266; hg19: chr13-103712499;