chr13-103066266-G-C

Position:

• chr13-103066266-G-C

Variant summary

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

The NM_000452.3(SLC10A2):​c.-17C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,588,744 control chromosomes in the GnomAD database, including 382 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 0.024 (64 hom., cov: 32)
  • Exomes 𝑓: 0.019 (318 hom.)
• Consequence: SLC10A2 NM_000452.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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=-0.94).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0242 (3684/152300) while in subpopulation AFR AF= 0.0362 (1503/41548). AF 95% confidence interval is 0.0347. There are 64 homozygotes in gnomad4. There are 1711 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3684 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.-17C>G		5_prime_UTR_variant	1/6	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.-17C>G		5_prime_UTR_variant	1/6	1	NM_000452.3	ENSP00000245312.3

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3685 AN: 152182 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0176 AC: 4150 AN: 235272 Hom.: 68 AF XY: 0.0171 AC XY: 2165 AN XY: 126364

Gnomad AFR exome AF: 0.0376

Gnomad AMR exome AF: 0.00797

Gnomad ASJ exome AF: 0.0594

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.00702

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.0189 AC: 27124 AN: 1436444 Hom.: 318 Cov.: 31 AF XY: 0.0188 AC XY: 13327 AN XY: 710632

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.00834

Gnomad4 ASJ exome AF: 0.0622

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00635

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0242 AC: 3684 AN: 152300 Hom.: 64 Cov.: 32 AF XY: 0.0230 AC XY: 1711 AN XY: 74468

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0250 Hom.: 44

Bravo AF: 0.0246

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.43

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: rs41281682; hg19: chr13-103718616;