rs6469675

chr8-117152910-A-G

Variant summary

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

The NM_173851.3(SLC30A8):c.272-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,456,850 control chromosomes in the GnomAD database, including 71,357 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 0.39 (14256 hom., cov: 32)
  • Exomes 𝑓: 0.29 (57101 hom.)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.272-34A>G		intron_variant		ENST00000456015.7
LOC105375716	XR_007061067.1	n.819+19705T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.272-34A>G		intron_variant		1	NM_173851.3	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58440 AN: 151820 Hom.: 14211 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.305 AC: 61828 AN: 202860 Hom.: 10989 AF XY: 0.297 AC XY: 32374 AN XY: 109060

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.380

Gnomad SAS exome AF: 0.291

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.285 AC: 371939 AN: 1304912 Hom.: 57101 Cov.: 28 AF XY: 0.284 AC XY: 180956 AN XY: 637736

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.385 AC: 58545 AN: 151938 Hom.: 14256 Cov.: 32 AF XY: 0.378 AC XY: 28093 AN XY: 74248

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.346

Alfa AF: 0.286 Hom.: 4368

Bravo AF: 0.404

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.63
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6469675; hg19: chr8-118165149; COSMIC: COSV69975167;