13-103046013-A-G

Variant names:

• chr13-103046013-A-G
• rs2301157
• NM_000452.3:c.*120T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.88).
• 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 rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.*120T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.*120T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_000452.3	ENSP00000245312.3

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

African (AFR) AF: 0.282 AC: 7132 AN: 25306

American (AMR) AF: 0.511 AC: 19511 AN: 38204

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 10123 AN: 22058

East Asian (EAS) AF: 0.377 AC: 13805 AN: 36618

South Asian (SAS) AF: 0.590 AC: 42920 AN: 72750

European-Finnish (FIN) AF: 0.562 AC: 27157 AN: 48300

Middle Eastern (MID) AF: 0.510 AC: 2476 AN: 4856

European-Non Finnish (NFE) AF: 0.562 AC: 446257 AN: 794642

Other (OTH) AF: 0.516 AC: 24406 AN: 47280

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

African (AFR) AF: 0.290 AC: 12039 AN: 41484

American (AMR) AF: 0.469 AC: 7165 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2024 AN: 5160

South Asian (SAS) AF: 0.579 AC: 2791 AN: 4822

European-Finnish (FIN) AF: 0.553 AC: 5829 AN: 10542

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37835 AN: 67958

Other (OTH) AF: 0.462 AC: 975 AN: 2112

Alfa AF: 0.521 Hom.: 70761

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
PhyloP100		-2.6
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: rs2301157; hg19: chr13-103698363; COSMIC: COSV55358513;