rs41281678

chr13-103052700-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000452.3(SLC10A2):c.505C>T(p.Leu169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,596,202 control chromosomes in the GnomAD database, including 561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (76 hom., cov: 32)
  • Exomes 𝑓: 0.024 (485 hom.)
• Consequence: SLC10A2 NM_000452.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 13-103052700-G-A is Benign according to our data. Variant chr13-103052700-G-A is described in ClinVar as [Benign]. Clinvar id is 501366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0263 (4001/152240) while in subpopulation AFR AF= 0.0401 (1664/41540). AF 95% confidence interval is 0.0385. There are 76 homozygotes in gnomad4. There are 1894 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 3990 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.505C>T	p.Leu169=	synonymous_variant	3/6	ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.505C>T	p.Leu169=	synonymous_variant	3/6	1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3990 AN: 152122 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.0194 AC: 4862 AN: 251120 Hom.: 67 AF XY: 0.0196 AC XY: 2655 AN XY: 135718

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0169

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0231

Gnomad FIN exome AF: 0.00883

Gnomad NFE exome AF: 0.0235

Gnomad OTH exome AF: 0.0203

GnomAD4 exome AF: 0.0238 AC: 34302 AN: 1443962 Hom.: 485 Cov.: 28 AF XY: 0.0237 AC XY: 17087 AN XY: 719578

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.00967

Gnomad4 NFE exome AF: 0.0254

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0263 AC: 4001 AN: 152240 Hom.: 76 Cov.: 32 AF XY: 0.0254 AC XY: 1894 AN XY: 74424

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0241 Hom.: 85

Bravo AF: 0.0275

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0254

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 11, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.5
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs41281678; hg19: chr13-103705050;