NM_000452.3:c.-17C>G

Variant names:

• chr13-103066266-G-C
• rs41281682
• NM_000452.3:c.-17C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.94).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.-17C>G		5_prime_UTR	Exon 1 of 6	NP_000443.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.-17C>G		5_prime_UTR	Exon 1 of 6	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

GnomAD2 exomes AF: 0.0176 AC: 4150 AN: 235272 AF XY: 0.0171

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 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

African (AFR) AF: 0.0387 AC: 1278 AN: 33018

American (AMR) AF: 0.00834 AC: 363 AN: 43508

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 1540 AN: 24748

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39340

South Asian (SAS) AF: 0.00635 AC: 526 AN: 82770

European-Finnish (FIN) AF: 0.0117 AC: 605 AN: 51922

Middle Eastern (MID) AF: 0.0347 AC: 182 AN: 5246

European-Non Finnish (NFE) AF: 0.0195 AC: 21387 AN: 1096678

Other (OTH) AF: 0.0210 AC: 1242 AN: 59214

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

African (AFR) AF: 0.0362 AC: 1503 AN: 41548

American (AMR) AF: 0.0127 AC: 195 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4832

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1469 AN: 68036

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.43
PhyloP100		0.0050
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	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: rs41281682; hg19: chr13-103718616;