rs41281680

chr13-103066121-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000452.3(SLC10A2):c.129C>T(p.Ala43=) 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

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 -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 id 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3691 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.129C>T	p.Ala43=	synonymous_variant	1/6	ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.129C>T	p.Ala43=	synonymous_variant	1/6	1	NM_000452.3	P1

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

GnomAD3 exomes AF: 0.0185 AC: 4649 AN: 251448 Hom.: 84 AF XY: 0.0178 AC XY: 2420 AN XY: 135892

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 SAS exome AF: 0.00719

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

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.00861

Gnomad4 ASJ exome AF: 0.0644

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00669

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0213

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

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0730

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0249 Hom.: 71

Bravo AF: 0.0246

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	5.0
Dann	Benign	0.59

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: rs41281680; hg19: chr13-103718471; COSMIC: COSV55358940;