rs41281678

Variant names:

• chr13-103052700-G-A
• rs41281678
• NM_000452.3:c.505C>T
• SLC10A2 p.Leu169Leu

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000452.3(SLC10A2):​c.505C>T​(p.Leu169Leu) 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:4
• Conservation: PhyloP100: 1.31
• Publications: 9 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 76 Unknown,AR gene

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.505C>T	p.Leu169Leu	synonymous	Exon 3 of 6	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.505C>T	p.Leu169Leu	synonymous	Exon 3 of 6	ENSP00000245312.3	Q12908

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

GnomAD2 exomes AF: 0.0194 AC: 4862 AN: 251120 AF XY: 0.0196

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 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

African (AFR) AF: 0.0426 AC: 1408 AN: 33032

American (AMR) AF: 0.0113 AC: 503 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 458 AN: 26010

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39612

South Asian (SAS) AF: 0.0238 AC: 2046 AN: 85890

European-Finnish (FIN) AF: 0.00967 AC: 516 AN: 53382

Middle Eastern (MID) AF: 0.0291 AC: 167 AN: 5740

European-Non Finnish (NFE) AF: 0.0254 AC: 27801 AN: 1095830

Other (OTH) AF: 0.0234 AC: 1401 AN: 59780

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

African (AFR) AF: 0.0401 AC: 1664 AN: 41540

American (AMR) AF: 0.0208 AC: 318 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4818

European-Finnish (FIN) AF: 0.0104 AC: 110 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1657 AN: 68022

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0248 Hom.: 128

Bravo AF: 0.0275

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0261

EpiControl AF: 0.0254

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41281678;

hg19: chr13-103705050;