13-103046280-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000452.3(SLC10A2):c.920-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,593,310 control chromosomes in the GnomAD database, including 608,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59115 hom., cov: 32)
  • Exomes 𝑓: 0.87 (549139 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0910

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-103046280-C-T is Benign according to our data. Variant chr13-103046280-C-T is described in ClinVar as [Benign]. Clinvar id is 1332970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-103046280-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.920-20G>A		intron_variant		ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.920-20G>A		intron_variant		1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133868 AN: 152120 Hom.: 59067 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.868

GnomAD3 exomes AF: 0.855 AC: 208955 AN: 244460 Hom.: 89772 AF XY: 0.858 AC XY: 113580 AN XY: 132310

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.760

Gnomad ASJ exome AF: 0.873

Gnomad EAS exome AF: 0.737

Gnomad SAS exome AF: 0.866

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.882

Gnomad OTH exome AF: 0.864

GnomAD4 exome AF: 0.872 AC: 1256485 AN: 1441072 Hom.: 549139 Cov.: 26 AF XY: 0.872 AC XY: 626012 AN XY: 718048

Gnomad4 AFR exome AF: 0.928

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.871

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.868

GnomAD4 genome AF: 0.880 AC: 133969 AN: 152238 Hom.: 59115 Cov.: 32 AF XY: 0.877 AC XY: 65251 AN XY: 74412

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.870

Alfa AF: 0.877 Hom.: 61917

Bravo AF: 0.876

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bile acid malabsorption, primary, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs279940; hg19: chr13-103698630;