rs279940

Variant names:

• chr13-103046280-C-T
• rs279940
• NM_000452.3:c.920-20G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-103046280-C-T
• chr13-103046280-C-A
• chr13-103046280-C-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.920-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,593,310 control chromosomes in the GnomAD database, including 608,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59115 hom., cov: 32)
  • Exomes 𝑓: 0.87 (549139 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0910
• Publications: 11 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-103046280-C-T is Benign according to our data. Variant chr13-103046280-C-T is described in ClinVar as Benign. ClinVar VariationId is 1332970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.920-20G>A		intron	N/A	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.920-20G>A		intron	N/A	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133868 AN: 152120 Hom.: 59067 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.868

GnomAD2 exomes AF: 0.855 AC: 208955 AN: 244460 AF XY: 0.858

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.760

Gnomad ASJ exome AF: 0.873

Gnomad EAS exome AF: 0.737

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.882

Gnomad OTH exome AF: 0.864

GnomAD4 exome AF: 0.872 AC: 1256485 AN: 1441072 Hom.: 549139 Cov.: 26 AF XY: 0.872 AC XY: 626012 AN XY: 718048

African (AFR) AF: 0.928 AC: 30551 AN: 32904

American (AMR) AF: 0.765 AC: 33915 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 22589 AN: 25924

East Asian (EAS) AF: 0.728 AC: 28620 AN: 39340

South Asian (SAS) AF: 0.865 AC: 74056 AN: 85608

European-Finnish (FIN) AF: 0.886 AC: 46847 AN: 52870

Middle Eastern (MID) AF: 0.870 AC: 4974 AN: 5718

European-Non Finnish (NFE) AF: 0.880 AC: 963228 AN: 1094826

Other (OTH) AF: 0.868 AC: 51705 AN: 59564

GnomAD4 genome AF: 0.880 AC: 133969 AN: 152238 Hom.: 59115 Cov.: 32 AF XY: 0.877 AC XY: 65251 AN XY: 74412

African (AFR) AF: 0.926 AC: 38493 AN: 41554

American (AMR) AF: 0.808 AC: 12347 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3013 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3828 AN: 5178

South Asian (SAS) AF: 0.849 AC: 4090 AN: 4818

European-Finnish (FIN) AF: 0.880 AC: 9328 AN: 10598

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59901 AN: 68018

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.877 Hom.: 100143

Bravo AF: 0.876

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bile acid malabsorption, primary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.17
PhyloP100		-0.091
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: rs279940; hg19: chr13-103698630;