rs41281680

Variant names:

• chr13-103066121-G-A
• rs41281680
• NM_000452.3:c.129C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-103066121-G-A
• chr13-103066121-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000452.3(SLC10A2):​c.129C>T​(p.Ala43Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,614,020 control chromosomes in the GnomAD database, including 402 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 (338 hom.)
• Consequence: SLC10A2 NM_000452.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.193
• Publications: 6 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-103066121-G-A is Benign according to our data. Variant chr13-103066121-G-A is described in ClinVar as Benign. ClinVar VariationId is 2122470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.193 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0242 (3690/152230) while in subpopulation AFR AF = 0.0361 (1500/41546). AF 95% confidence interval is 0.0346. There are 64 homozygotes in GnomAd4. There are 1712 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.129C>T	p.Ala43Ala	synonymous	Exon 1 of 6	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.129C>T	p.Ala43Ala	synonymous	Exon 1 of 6	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3691 AN: 152110 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0240

GnomAD2 exomes AF: 0.0185 AC: 4649 AN: 251448 AF XY: 0.0178

Gnomad AFR exome AF: 0.0378

Gnomad AMR exome AF: 0.00824

Gnomad ASJ exome AF: 0.0640

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0222

GnomAD4 exome AF: 0.0192 AC: 28125 AN: 1461790 Hom.: 338 Cov.: 31 AF XY: 0.0191 AC XY: 13914 AN XY: 727200

African (AFR) AF: 0.0388 AC: 1300 AN: 33480

American (AMR) AF: 0.00861 AC: 385 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0644 AC: 1683 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00669 AC: 577 AN: 86258

European-Finnish (FIN) AF: 0.0118 AC: 632 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0198 AC: 22054 AN: 1111950

Other (OTH) AF: 0.0213 AC: 1284 AN: 60372

GnomAD4 genome AF: 0.0242 AC: 3690 AN: 152230 Hom.: 64 Cov.: 32 AF XY: 0.0230 AC XY: 1712 AN XY: 74440

African (AFR) AF: 0.0361 AC: 1500 AN: 41546

American (AMR) AF: 0.0128 AC: 196 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3468

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

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4830

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

Middle Eastern (MID) AF: 0.0552 AC: 16 AN: 290

European-Non Finnish (NFE) AF: 0.0217 AC: 1477 AN: 68008

Other (OTH) AF: 0.0237 AC: 50 AN: 2106

Alfa AF: 0.0248 Hom.: 99

Bravo AF: 0.0246

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	-0.76
CADD	Benign	5.0
DANN	Benign	0.59
PhyloP100		-0.19
PromoterAI		0.0038	Neutral
Mutation Taster		=97/3	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: rs41281680; hg19: chr13-103718471; COSMIC: COSV55358940;