rs73069071

Positions:

• chr12-21357370-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307378.10(SLCO1A2):​c.-63+17029A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,052 control chromosomes in the GnomAD database, including 1,639 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 0.14 (1639 hom., cov: 32)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IAPP	NM_001329201.2	c.-16+2357T>C		intron_variant
SLCO1A2	NM_001386878.1	c.-62-22661A>G		intron_variant
SLCO1A2	NM_001386881.1	c.-57-22666A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-63+17029A>G		intron_variant		1		P1
SLCO1A2	ENST00000413682.5	c.-311-22666A>G		intron_variant		4
SLCO1A2	ENST00000416627.1	c.-63+17029A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21420 AN: 151934 Hom.: 1628 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.141 AC: 21467 AN: 152052 Hom.: 1639 Cov.: 32 AF XY: 0.139 AC XY: 10323 AN XY: 74326

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.158

Alfa AF: 0.133 Hom.: 166

Bravo AF: 0.145

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	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: rs73069071; hg19: chr12-21510304;