ENST00000307378.10:c.-63+1727T>G

Variant names:

• chr12-21372672-A-C
• rs7137767
• ENST00000307378.10:c.-63+1727T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307378.10(SLCO1A2):​c.-63+1727T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,090 control chromosomes in the GnomAD database, including 15,123 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 0.44 (15123 hom., cov: 33)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 8 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IAPP	NM_000415.3	c.-348A>C		upstream_gene_variant		ENST00000240652.8	NP_000406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IAPP	ENST00000240652.8	c.-348A>C		upstream_gene_variant		1	NM_000415.3	ENSP00000240652.3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67308 AN: 151972 Hom.: 15118 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.443 AC: 67339 AN: 152090 Hom.: 15123 Cov.: 33 AF XY: 0.435 AC XY: 32373 AN XY: 74346

African (AFR) AF: 0.482 AC: 20005 AN: 41470

American (AMR) AF: 0.402 AC: 6140 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2006 AN: 5176

South Asian (SAS) AF: 0.435 AC: 2097 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3151 AN: 10580

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30561 AN: 67996

Other (OTH) AF: 0.449 AC: 949 AN: 2114

Alfa AF: 0.454 Hom.: 26778

Bravo AF: 0.454

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		0.23
PromoterAI		0.013	Neutral
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: rs7137767; hg19: chr12-21525606;