rs4646296

Variant names:

• chr14-69776788-C-G
• rs4646296
• NM_003049.4:c.944-400G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003049.4(SLC10A1):​c.944-400G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 152,288 control chromosomes in the GnomAD database, including 429 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 0.064 (429 hom., cov: 32)
• Consequence: SLC10A1 NM_003049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 9 publications found

Genes affected

SLC10A1 (HGNC:10905): (solute carrier family 10 member 1) The protein encoded by this gene belongs to the sodium/bile acid cotransporter family, which are integral membrane glycoproteins that participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids; the ileal sodium/bile acid cotransporter with an apical cell localization that absorbs bile acids from the intestinal lumen, bile duct and kidney, and the liver-specific sodium/bile acid cotransporter, represented by this protein, that is found in the basolateral membranes of hepatocytes. Bile acids are the catabolic product of cholesterol metabolism, hence this protein is important for cholesterol homeostasis. [provided by RefSeq, Oct 2011]

SLC10A1 Gene-Disease associations (from GenCC):

• hypercholanemia, familial, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003049.4. 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
	SLC10A1	NM_003049.4	MANE Select	c.944-400G>C		intron	N/A	NP_003040.1	Q14973

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A1	ENST00000216540.5	TSL:1 MANE Select	c.944-400G>C		intron	N/A	ENSP00000216540.4	Q14973
	SLC10A1	ENST00000871518.1		c.995-400G>C		intron	N/A	ENSP00000541577.1
	SLC10A1	ENST00000871519.1		c.980-400G>C		intron	N/A	ENSP00000541578.1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9757 AN: 152170 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0641 AC: 9758 AN: 152288 Hom.: 429 Cov.: 32 AF XY: 0.0688 AC XY: 5123 AN XY: 74450

African (AFR) AF: 0.0143 AC: 596 AN: 41574

American (AMR) AF: 0.0490 AC: 750 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.0844 AC: 437 AN: 5178

South Asian (SAS) AF: 0.0657 AC: 317 AN: 4828

European-Finnish (FIN) AF: 0.167 AC: 1763 AN: 10580

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5541 AN: 68030

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0706 Hom.: 62

Bravo AF: 0.0545

Asia WGS AF: 0.0520 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.38
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4646296; hg19: chr14-70243505;