13-103046013-A-G

Position:

• chr13-103046013-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000452.3(SLC10A2):​c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,242,032 control chromosomes in the GnomAD database, including 181,185 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 0.47 (17435 hom., cov: 32)
  • Exomes 𝑓: 0.54 (163750 hom.)
• Consequence: SLC10A2 NM_000452.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.*120T>C		3_prime_UTR_variant	6/6	ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.*120T>C		3_prime_UTR_variant	6/6	1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70685 AN: 151900 Hom.: 17428 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.545 AC: 593787 AN: 1090014 Hom.: 163750 Cov.: 13 AF XY: 0.547 AC XY: 302920 AN XY: 553672

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.465 AC: 70713 AN: 152018 Hom.: 17435 Cov.: 32 AF XY: 0.465 AC XY: 34578 AN XY: 74294

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.462

Alfa AF: 0.537 Hom.: 44896

Bravo AF: 0.451

Asia WGS AF: 0.455 AC: 1584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.59

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: rs2301157; hg19: chr13-103698363; COSMIC: COSV55358513;