rs60571683

Variant names:

• chr12-20916115-G-A
• rs60571683
• NM_019844.4:c.1977G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019844.4(SLCO1B3):​c.1977G>A​(p.Ser659Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 1,612,444 control chromosomes in the GnomAD database, including 2,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (177 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2106 hom.)
• Consequence: SLCO1B3 NM_019844.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.782
• Publications: 14 publications found

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

LOC124902894 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-20916115-G-A is Benign according to our data. Variant chr12-20916115-G-A is described in ClinVar as Benign. ClinVar VariationId is 307914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.782 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. 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
	SLCO1B3	NM_019844.4	MANE Select	c.1977G>A	p.Ser659Ser	synonymous	Exon 16 of 16	NP_062818.1	Q9NPD5-1
	SLCO1B3	NM_001349920.2		c.1893G>A	p.Ser631Ser	synonymous	Exon 14 of 14	NP_001336849.1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.1865+14648G>A		intron	N/A	NP_001358026.1	A0A0A6YYJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.1977G>A	p.Ser659Ser	synonymous	Exon 16 of 16	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3	ENST00000261196.6	TSL:1	c.1977G>A	p.Ser659Ser	synonymous	Exon 14 of 14	ENSP00000261196.2	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.1865+14648G>A		intron	N/A	ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5836 AN: 151990 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0436

GnomAD2 exomes AF: 0.0379 AC: 9487 AN: 250602 AF XY: 0.0380

Gnomad AFR exome AF: 0.00875

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.000328

Gnomad FIN exome AF: 0.0123

Gnomad NFE exome AF: 0.0555

Gnomad OTH exome AF: 0.0520

GnomAD4 exome AF: 0.0486 AC: 70986 AN: 1460338 Hom.: 2106 Cov.: 30 AF XY: 0.0477 AC XY: 34644 AN XY: 726514

African (AFR) AF: 0.00804 AC: 269 AN: 33456

American (AMR) AF: 0.0415 AC: 1855 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 2343 AN: 26112

East Asian (EAS) AF: 0.000278 AC: 11 AN: 39542

South Asian (SAS) AF: 0.00885 AC: 763 AN: 86214

European-Finnish (FIN) AF: 0.0144 AC: 769 AN: 53398

Middle Eastern (MID) AF: 0.0273 AC: 157 AN: 5754

European-Non Finnish (NFE) AF: 0.0556 AC: 61779 AN: 1110838

Other (OTH) AF: 0.0504 AC: 3040 AN: 60340

GnomAD4 genome AF: 0.0383 AC: 5830 AN: 152106 Hom.: 177 Cov.: 32 AF XY: 0.0361 AC XY: 2683 AN XY: 74352

African (AFR) AF: 0.0107 AC: 445 AN: 41516

American (AMR) AF: 0.0607 AC: 927 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4820

European-Finnish (FIN) AF: 0.0112 AC: 118 AN: 10560

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3811 AN: 67988

Other (OTH) AF: 0.0427 AC: 90 AN: 2110

Alfa AF: 0.0513 Hom.: 250

Bravo AF: 0.0415

Asia WGS AF: 0.00405 AC: 14 AN: 3474

EpiCase AF: 0.0595

EpiControl AF: 0.0643

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Rotor syndrome (2)
-	-	1	not provided (1)
-	-	1	SLCO1B3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		-0.78
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: rs60571683; hg19: chr12-21069049;