NM_003049.4:c.944-708A>C

Variant names:

• chr14-69777096-T-G
• rs9323529
• NM_003049.4:c.944-708A>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.944-708A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,256 control chromosomes in the GnomAD database, including 2,118 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 0.095 (2118 hom., cov: 32)
• Consequence: SLC10A1 NM_003049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 4 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: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A1	NM_003049.4	MANE Select	c.944-708A>C		intron	N/A	NP_003040.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A1	ENST00000216540.5	TSL:1 MANE Select	c.944-708A>C		intron	N/A	ENSP00000216540.4

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14352 AN: 152138 Hom.: 2098 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0946 AC: 14410 AN: 152256 Hom.: 2118 Cov.: 32 AF XY: 0.0911 AC XY: 6787 AN XY: 74478

African (AFR) AF: 0.312 AC: 12951 AN: 41496

American (AMR) AF: 0.0442 AC: 677 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00578 AC: 393 AN: 68020

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0402 Hom.: 429

Bravo AF: 0.107

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.54
PhyloP100		0.32
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: rs9323529; hg19: chr14-70243813;