rs183963

Variant names:

• chr13-103054934-T-A
• rs183963
• NM_000452.3:c.497-2226A>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.497-2226A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,980 control chromosomes in the GnomAD database, including 14,131 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 0.42 (14131 hom., cov: 32)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 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.497-2226A>T		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.497-2226A>T		intron	N/A	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64254 AN: 151862 Hom.: 14110 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.423 AC: 64318 AN: 151980 Hom.: 14131 Cov.: 32 AF XY: 0.422 AC XY: 31359 AN XY: 74252

African (AFR) AF: 0.542 AC: 22444 AN: 41426

American (AMR) AF: 0.367 AC: 5596 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3472

East Asian (EAS) AF: 0.346 AC: 1790 AN: 5174

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4816

European-Finnish (FIN) AF: 0.369 AC: 3884 AN: 10538

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25535 AN: 67982

Other (OTH) AF: 0.427 AC: 899 AN: 2106

Alfa AF: 0.402 Hom.: 1853

Bravo AF: 0.423

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs183963; hg19: chr13-103707284; COSMIC: COSV107306840;