Genetic Variant SLC10A2:c.378-105A>G (chr13-103058487-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000452.3(SLC10A2):c.378-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 734,904 control chromosomes in the GnomAD database, including 55,859 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 0.41 ( 12974 hom., cov: 31)

Exomes 𝑓: 0.38 ( 42885 hom. )

Consequence

SLC10A2
NM_000452.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.693

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

bile acid malabsorption, primary, 1
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC10A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.378-105A>G		intron_variant	Intron 1 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.378-105A>G		intron_variant	Intron 1 of 5	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61982

AN:

151898

Hom.:

12953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.378

AC:

220118

AN:

582888

Hom.:

42885

AF XY:

0.380

AC XY:

119219

AN XY:

313912

show subpopulations

African (AFR)

AF:

0.493

AC:

7729

AN:

15684

American (AMR)

AF:

0.277

AC:

9438

AN:

34104

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

9791

AN:

19802

East Asian (EAS)

AF:

0.342

AC:

10855

AN:

31774

South Asian (SAS)

AF:

0.399

AC:

24636

AN:

61718

European-Finnish (FIN)

AF:

0.373

AC:

16718

AN:

44816

Middle Eastern (MID)

AF:

0.436

AC:

1075

AN:

2464

European-Non Finnish (NFE)

AF:

0.373

AC:

127542

AN:

341602

Other (OTH)

AF:

0.399

AC:

12334

AN:

30924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7503

15006

22510

30013

37516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1012

2024

3036

4048

5060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.408

AC:

62044

AN:

152016

Hom.:

12974

Cov.:

AF XY:

0.408

AC XY:

30310

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.490

AC:

20317

AN:

41444

American (AMR)

AF:

0.359

AC:

5484

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1709

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1772

AN:

5178

South Asian (SAS)

AF:

0.388

AC:

1867

AN:

4816

European-Finnish (FIN)

AF:

0.370

AC:

3905

AN:

10568

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25504

AN:

67954

Other (OTH)

AF:

0.422

AC:

890

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1864

3728

5591

7455

9319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.395

Hom.:

3540

Bravo

AF:

0.406

Asia WGS

AF:

0.376

AC:

1309

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

(source)

DANN

Benign

0.58

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over