rs924922

Positions:

• chr8-117157479-G-A

Variant summary

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

The NM_173851.3(SLC30A8):​c.419-212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,092 control chromosomes in the GnomAD database, including 14,142 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 0.38 (14142 hom., cov: 32)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.419-212G>A		intron_variant		ENST00000456015.7
LOC105375716	XR_007061067.1	n.819+15136C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.419-212G>A		intron_variant		1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.272-212G>A		intron_variant		1
SLC30A8	ENST00000521243.5	c.272-212G>A		intron_variant		1
SLC30A8	ENST00000427715.2	c.272-212G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58087 AN: 151974 Hom.: 14097 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.383 AC: 58192 AN: 152092 Hom.: 14142 Cov.: 32 AF XY: 0.376 AC XY: 27937 AN XY: 74346

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.340

Alfa AF: 0.319 Hom.: 1175

Bravo AF: 0.401

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.37

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: rs924922; hg19: chr8-118169718; COSMIC: COSV69974034; COSMIC: COSV69974034;