rs4646296

chr14-69776788-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A1	NM_003049.4	c.944-400G>C		intron_variant		ENST00000216540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A1	ENST00000216540.5	c.944-400G>C		intron_variant		1	NM_003049.4	P1

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

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.0844

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.0625

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.1
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646296; hg19: chr14-70243505;