Genetic Variant SLCO1A2:c.-63+15136A>C (chr12-21359263-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134431.5(SLCO1A2):c.-63+15136A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,184 control chromosomes in the GnomAD database, including 1,050 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 0.094 ( 1050 hom., cov: 32)

Consequence

SLCO1A2
NM_134431.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

3 publications found

Variant links:

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

SLCO1A2 links:

IAPP (HGNC:5329): (islet amyloid polypeptide) This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity. [provided by RefSeq, Jul 2016]

IAPP links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134431.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
SLCO1A2	NM_001386878.1	c.-62-24554A>C	intron	N/A	NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-24559A>C	intron	N/A	NP_001373810.1
SLCO1A2	NM_001386882.2	c.-63+1400A>C	intron	N/A	NP_001373811.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLCO1A2	ENST00000307378.10	TSL:1	c.-63+15136A>C	intron	N/A	ENSP00000305974.6
SLCO1A2	ENST00000938257.1		c.-57-24559A>C	intron	N/A	ENSP00000608316.1
SLCO1A2	ENST00000938258.1		c.-57-24559A>C	intron	N/A	ENSP00000608317.1

Frequencies

GnomAD3 genomes

AF:

0.0940

AC:

14294

AN:

152066

Hom.:

1052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0665

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0718

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

GnomAD4 genome

AF:

0.0939

AC:

14284

AN:

152184

Hom.:

1050

Cov.:

AF XY:

0.102

AC XY:

7586

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0571

AC:

2370

AN:

41538

American (AMR)

AF:

0.0663

AC:

1014

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3472

East Asian (EAS)

AF:

0.402

AC:

2079

AN:

5168

South Asian (SAS)

AF:

0.173

AC:

837

AN:

4828

European-Finnish (FIN)

AF:

0.208

AC:

2200

AN:

10568

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5416

AN:

68000

Other (OTH)

AF:

0.0739

AC:

156

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

626

1252

1878

2504

3130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0744

Hom.:

841

Bravo

AF:

0.0798

Asia WGS

AF:

0.247

AC:

858

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.4

(source)

DANN

Benign

0.84

PhyloP100

0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over