rs56182000

Variant names:

• chr13-103065861-A-G
• rs56182000
• NM_000452.3:c.377+12T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-103065861-A-G
• chr13-103065861-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000452.3(SLC10A2):​c.377+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,613,718 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (64 hom., cov: 32)
  • Exomes 𝑓: 0.019 (337 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.640
• Publications: 2 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-103065861-A-G is Benign according to our data. Variant chr13-103065861-A-G is described in ClinVar as Benign. ClinVar VariationId is 1970991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0241 (3678/152316) while in subpopulation AFR AF = 0.0361 (1499/41566). AF 95% confidence interval is 0.0345. There are 64 homozygotes in GnomAd4. There are 1706 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 Unknown,AR 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.377+12T>C		intron	N/A	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.377+12T>C		intron	N/A	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3679 AN: 152198 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.0185 AC: 4635 AN: 250878 AF XY: 0.0178

Gnomad AFR exome AF: 0.0378

Gnomad AMR exome AF: 0.00821

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0222

GnomAD4 exome AF: 0.0192 AC: 28092 AN: 1461402 Hom.: 337 Cov.: 31 AF XY: 0.0191 AC XY: 13897 AN XY: 727042

African (AFR) AF: 0.0388 AC: 1298 AN: 33474

American (AMR) AF: 0.00847 AC: 379 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 1683 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00669 AC: 577 AN: 86244

European-Finnish (FIN) AF: 0.0118 AC: 629 AN: 53248

Middle Eastern (MID) AF: 0.0362 AC: 209 AN: 5766

European-Non Finnish (NFE) AF: 0.0198 AC: 22032 AN: 1111734

Other (OTH) AF: 0.0213 AC: 1284 AN: 60386

GnomAD4 genome AF: 0.0241 AC: 3678 AN: 152316 Hom.: 64 Cov.: 32 AF XY: 0.0229 AC XY: 1706 AN XY: 74476

African (AFR) AF: 0.0361 AC: 1499 AN: 41566

American (AMR) AF: 0.0123 AC: 188 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4828

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0217 AC: 1476 AN: 68030

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0207 Hom.: 17

Bravo AF: 0.0245

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.10
DANN	Benign	0.51
PhyloP100		-0.64
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: rs56182000; hg19: chr13-103718211;