rs2296651

Positions:

• chr14-69778476-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003049.4(SLC10A1):​c.800C>T​(p.Ser267Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00173 in 1,613,510 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (18 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (148 hom.)
• Consequence: SLC10A1 NM_003049.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:3
• Conservation: PhyloP100: 5.56

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052731335).
• BP6: Variant 14-69778476-G-A is Benign according to our data. Variant chr14-69778476-G-A is described in ClinVar as [Benign]. Clinvar id is 501461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-69778476-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A1	NM_003049.4	c.800C>T	p.Ser267Phe	missense_variant	4/5	ENST00000216540.5	NP_003040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A1	ENST00000216540.5	c.800C>T	p.Ser267Phe	missense_variant	4/5	1	NM_003049.4	ENSP00000216540.4

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 152184 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00629 AC: 1579 AN: 250862 Hom.: 100 AF XY: 0.00558 AC XY: 756 AN XY: 135604

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0830

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00160 AC: 2340 AN: 1461208 Hom.: 148 Cov.: 31 AF XY: 0.00141 AC XY: 1027 AN XY: 726962

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.000314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0427

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00983

GnomAD4 genome AF: 0.00295 AC: 449 AN: 152302 Hom.: 18 Cov.: 31 AF XY: 0.00299 AC XY: 223 AN XY: 74462

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0702

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00203 Hom.: 23

Bravo AF: 0.00363

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00568 AC: 689

Asia WGS AF: 0.0230 AC: 78 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypercholanemia, familial, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 04, 2024

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 18, 2017

- -

Hepatitis B virus, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 04, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.012	D
Polyphen		0.96	D
Vest4		0.52
MVP		0.79
MPC		0.0023
ClinPred		0.034	T
GERP RS		4.8
Varity_R		0.16
gMVP		0.80

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: rs2296651; hg19: chr14-70245193;