rs7002176

Positions:

• chr8-117169811-T-A
• chr8-117169811-T-G

Variant summary

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

The NM_173851.3(SLC30A8):​c.830-1223T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,774 control chromosomes in the GnomAD database, including 13,211 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 0.41 (13211 hom., cov: 31)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.830-1223T>A		intron_variant		ENST00000456015.7
LOC105375716	XR_007061067.1	n.819+2804A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.830-1223T>A		intron_variant		1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.683-1223T>A		intron_variant		1
SLC30A8	ENST00000521243.5	c.683-1223T>A		intron_variant		1
SLC30A8	ENST00000427715.2	c.683-1223T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61586 AN: 151656 Hom.: 13196 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.406 AC: 61641 AN: 151774 Hom.: 13211 Cov.: 31 AF XY: 0.404 AC XY: 29931 AN XY: 74128

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.417

Alfa AF: 0.220 Hom.: 465

Bravo AF: 0.419

Asia WGS AF: 0.419 AC: 1457 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	2.9
DANN	Benign	0.75

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: rs7002176; hg19: chr8-118182050;