rs66842575

Variant names:

• chr13-103052748-T-A
• rs66842575
• NM_000452.3:c.497-40A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000452.3(SLC10A2):​c.497-40A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,241,754 control chromosomes in the GnomAD database, including 344 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 0.025 (61 hom., cov: 32)
  • Exomes 𝑓: 0.019 (283 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0247 (3743/151764) while in subpopulation AFR AF = 0.0371 (1535/41366). AF 95% confidence interval is 0.0356. There are 61 homozygotes in GnomAd4. There are 1734 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.497-40A>T		intron_variant	Intron 2 of 5	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.497-40A>T		intron_variant	Intron 2 of 5	1	NM_000452.3	ENSP00000245312.3

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3743 AN: 151646 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00378

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.0186 AC: 4633 AN: 249404 AF XY: 0.0178

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.00908

Gnomad ASJ exome AF: 0.0669

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.0219

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0187 AC: 20338 AN: 1089990 Hom.: 283 Cov.: 15 AF XY: 0.0185 AC XY: 10374 AN XY: 559736

African (AFR) AF: 0.0408 AC: 1051 AN: 25778

American (AMR) AF: 0.00932 AC: 412 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 1594 AN: 23858

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38042

South Asian (SAS) AF: 0.00441 AC: 348 AN: 78914

European-Finnish (FIN) AF: 0.0117 AC: 619 AN: 53068

Middle Eastern (MID) AF: 0.0368 AC: 185 AN: 5030

European-Non Finnish (NFE) AF: 0.0195 AC: 15071 AN: 772878

Other (OTH) AF: 0.0219 AC: 1057 AN: 48232

GnomAD4 genome AF: 0.0247 AC: 3743 AN: 151764 Hom.: 61 Cov.: 32 AF XY: 0.0234 AC XY: 1734 AN XY: 74164

African (AFR) AF: 0.0371 AC: 1535 AN: 41366

American (AMR) AF: 0.0128 AC: 195 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00358 AC: 17 AN: 4752

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10566

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0221 AC: 1502 AN: 67902

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0296 Hom.: 22

Bravo AF: 0.0251

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.49
PhyloP100		-0.71
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: rs66842575; hg19: chr13-103705098;