rs1329516

chr13-103065764-A-G

Variant summary

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

The NM_000452.3(SLC10A2):c.377+109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,232,004 control chromosomes in the GnomAD database, including 75 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 0.011 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (31 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1739/152306) while in subpopulation AFR AF= 0.0396 (1645/41562). AF 95% confidence interval is 0.038. There are 44 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1731 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.377+109T>C		intron_variant		ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.377+109T>C		intron_variant		1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1731 AN: 152188 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00129 AC: 1394 AN: 1079698 Hom.: 31 AF XY: 0.00109 AC XY: 606 AN XY: 554372

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.0000420

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000899

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000645

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.0114 AC: 1739 AN: 152306 Hom.: 44 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74510

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00484 Hom.: 2

Bravo AF: 0.0128

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.9
Dann	Benign	0.60

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: rs1329516; hg19: chr13-103718114;