13-103051229-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000452.3(SLC10A2):c.761+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,608,310 control chromosomes in the GnomAD database, including 234,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16848 hom., cov: 31)
  • Exomes 𝑓: 0.54 (217518 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-103051229-T-C is Benign according to our data. Variant chr13-103051229-T-C is described in ClinVar as [Benign]. Clinvar id is 1332971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.761+28A>G		intron_variant		ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.761+28A>G		intron_variant		1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68492 AN: 151808 Hom.: 16847 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.516 AC: 128438 AN: 249022 Hom.: 34325 AF XY: 0.525 AC XY: 70766 AN XY: 134830

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.587

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.542 AC: 789445 AN: 1456384 Hom.: 217518 Cov.: 31 AF XY: 0.544 AC XY: 394672 AN XY: 724934

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.561

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.451 AC: 68496 AN: 151926 Hom.: 16848 Cov.: 31 AF XY: 0.452 AC XY: 33549 AN XY: 74272

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.447

Alfa AF: 0.496 Hom.: 4880

Bravo AF: 0.435

Asia WGS AF: 0.448 AC: 1562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bile acid malabsorption, primary, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.3
Dann	Benign	0.72

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: rs8000956; hg19: chr13-103703579; COSMIC: COSV55358521;