Genetic Variant SLC10A2:c.761+28A>G (chr13-103051229-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0490

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.761+28A>G		intron_variant	Intron 4 of 5	ENST00000245312.5	NP_000443.2	Q12908

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 link	c.761+28A>G		intron_variant	Intron 4 of 5	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68492

AN:

151808

Hom.:

16847

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.544

AC XY:

394672

AN XY:

724934

show subpopulations

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.:

AF XY:

0.452

AC XY:

33549

AN XY:

74272

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bile acid malabsorption, primary, 1

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over