rs2464592

Positions:

• chr8-117171312-G-A
• chr8-117171312-G-C
• chr8-117171312-G-T

Variant summary

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

The NM_173851.3(SLC30A8):​c.964+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 886,660 control chromosomes in the GnomAD database, including 215,089 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 0.60 (29870 hom., cov: 31)
  • Exomes 𝑓: 0.71 (185219 hom.)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

Genes affected

SLC30A8 (HGNC:20303): (solute carrier family 30 member 8) The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

LOC105375716 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.964+144G>A		intron_variant		ENST00000456015.7
LOC105375716	XR_007061067.1	n.819+1303C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.964+144G>A		intron_variant		1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.817+144G>A		intron_variant		1
SLC30A8	ENST00000521243.5	c.817+144G>A		intron_variant		1
SLC30A8	ENST00000427715.2	c.817+144G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90894 AN: 151638 Hom.: 29859 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.604

GnomAD4 exome AF: 0.706 AC: 518599 AN: 734904 Hom.: 185219 AF XY: 0.705 AC XY: 272127 AN XY: 386146

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.714

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.599 AC: 90932 AN: 151756 Hom.: 29870 Cov.: 31 AF XY: 0.606 AC XY: 44926 AN XY: 74132

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.605

Alfa AF: 0.689 Hom.: 61212

Bravo AF: 0.580

Asia WGS AF: 0.668 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.6
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2464592; hg19: chr8-118183551; COSMIC: COSV69969297;