rs66842575

Positions:

• chr13-103052748-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000245312.5(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 ENST00000245312.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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 -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.497-40A>T		intron_variant		ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.497-40A>T		intron_variant		1	NM_000452.3	ENSP00000245312	P1

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

GnomAD3 exomes AF: 0.0186 AC: 4633 AN: 249404 Hom.: 76 AF XY: 0.0178 AC XY: 2395 AN XY: 134794

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 SAS exome AF: 0.00446

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

Gnomad4 AFR exome AF: 0.0408

Gnomad4 AMR exome AF: 0.00932

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0000263

Gnomad4 SAS exome AF: 0.00441

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0219

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

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00358

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0237

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs66842575; hg19: chr13-103705098;