13-103051229-T-C

Variant names:

• chr13-103051229-T-C
• rs8000956
• NM_000452.3:c.761+28A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0490
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.761+28A>G		intron_variant	Intron 4 of 5	ENST00000245312.5	NP_000443.2

Ensembl

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

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

GnomAD2 exomes AF: 0.516 AC: 128438 AN: 249022 AF XY: 0.525

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 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

African (AFR) AF: 0.227 AC: 7587 AN: 33380

American (AMR) AF: 0.508 AC: 22711 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 11891 AN: 26102

East Asian (EAS) AF: 0.378 AC: 14998 AN: 39658

South Asian (SAS) AF: 0.586 AC: 50452 AN: 86162

European-Finnish (FIN) AF: 0.561 AC: 29556 AN: 52672

Middle Eastern (MID) AF: 0.499 AC: 2873 AN: 5760

European-Non Finnish (NFE) AF: 0.558 AC: 618624 AN: 1107732

Other (OTH) AF: 0.511 AC: 30753 AN: 60214

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

African (AFR) AF: 0.243 AC: 10066 AN: 41464

American (AMR) AF: 0.465 AC: 7100 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2030 AN: 5148

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4816

European-Finnish (FIN) AF: 0.553 AC: 5833 AN: 10548

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37706 AN: 67912

Other (OTH) AF: 0.447 AC: 940 AN: 2102

Alfa AF: 0.488 Hom.: 13685

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

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
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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