dbSNP rs16961281: SLC10A2:c.-225C>T (chr13-103066474-G-A) – 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.-225C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 459,014 control chromosomes in the GnomAD database, including 1,429 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 0.081 ( 553 hom., cov: 32)

Exomes 𝑓: 0.072 ( 876 hom. )

Consequence

SLC10A2
NM_000452.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.974

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:

Genome browser will be placed here

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=-0.6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.-225C>T		upstream_gene_variant		ENST00000245312.5	NP_000443.2	Q12908

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 link	c.-225C>T		upstream_gene_variant		1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.0807

AC:

12278

AN:

152132

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.0571

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0634

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.0789

GnomAD4 exome

AF:

0.0720

AC:

22089

AN:

306764

Hom.:

876

Cov.:

AF XY:

0.0715

AC XY:

11178

AN XY:

156282

show subpopulations

African (AFR)

AF:

0.121

AC:

1221

AN:

10112

American (AMR)

AF:

0.0490

AC:

550

AN:

11226

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

1235

AN:

10462

East Asian (EAS)

AF:

0.0571

AC:

1493

AN:

26164

South Asian (SAS)

AF:

0.0581

AC:

672

AN:

11560

European-Finnish (FIN)

AF:

0.101

AC:

2157

AN:

21356

Middle Eastern (MID)

AF:

0.0735

AC:

112

AN:

1524

European-Non Finnish (NFE)

AF:

0.0671

AC:

13070

AN:

194870

Other (OTH)

AF:

0.0810

AC:

1579

AN:

19490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

956

1911

2867

3822

4778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0807

AC:

12294

AN:

152250

Hom.:

553

Cov.:

AF XY:

0.0818

AC XY:

6087

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.114

AC:

4737

AN:

41544

American (AMR)

AF:

0.0569

AC:

871

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

406

AN:

3466

East Asian (EAS)

AF:

0.0637

AC:

330

AN:

5180

South Asian (SAS)

AF:

0.0456

AC:

220

AN:

4826

European-Finnish (FIN)

AF:

0.106

AC:

1117

AN:

10580

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0646

AC:

4393

AN:

68026

Other (OTH)

AF:

0.0785

AC:

166

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

595

1189

1784

2378

2973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0683

Hom.:

746

Bravo

AF:

0.0784

Asia WGS

AF:

0.0580

AC:

203

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.2

(source)

DANN

Benign

0.67

PhyloP100

0.97

PromoterAI

-0.0038

Neutral

(source)

Mutation Taster

=300/0

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