rs183963

chr13-103054934-T-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.497-2226A>T		intron_variant		ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.497-2226A>T		intron_variant		1	NM_000452.3	P1

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

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.427

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs183963; hg19: chr13-103707284;