rs61745930

chr14-69779260-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003049.4(SLC10A1):c.668T>C(p.Ile223Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00209 in 1,613,984 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: SLC10A1 NM_003049.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004248649).
• BP6: Variant 14-69779260-A-G is Benign according to our data. Variant chr14-69779260-A-G is described in ClinVar as [Benign]. Clinvar id is 781133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1749/152208) while in subpopulation AFR AF= 0.0404 (1678/41528). AF 95% confidence interval is 0.0388. There are 37 homozygotes in gnomad4. There are 808 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A1	NM_003049.4	c.668T>C	p.Ile223Thr	missense_variant	3/5	ENST00000216540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A1	ENST00000216540.5	c.668T>C	p.Ile223Thr	missense_variant	3/5	1	NM_003049.4	P1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1751 AN: 152100 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00290 AC: 729 AN: 251106 Hom.: 12 AF XY: 0.00205 AC XY: 278 AN XY: 135712

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00111 AC: 1626 AN: 1461776 Hom.: 33 Cov.: 33 AF XY: 0.000949 AC XY: 690 AN XY: 727182

Gnomad4 AFR exome AF: 0.0415

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.0115 AC: 1749 AN: 152208 Hom.: 37 Cov.: 32 AF XY: 0.0109 AC XY: 808 AN XY: 74422

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.00282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00192 Hom.: 8

Bravo AF: 0.0132

ESP6500AA AF: 0.0379 AC: 167

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00347 AC: 421

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	22
Dann	Benign	0.92
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.093
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.042	D
Polyphen		0.017	B
Vest4		0.36
MVP		0.33
MPC		0.0013
ClinPred		0.038	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.77

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: rs61745930; hg19: chr14-70245977;