chr8-117000026-G-A

Variant names:

• chr8-117000026-G-A
• rs2938864
• ENST00000521243.5:c.-107+48907G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521243.5(SLC30A8):​c.-107+48907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,892 control chromosomes in the GnomAD database, including 11,944 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 (11944 hom., cov: 31)
• Consequence: SLC30A8 ENST00000521243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A8	NM_001172811.2	c.-107+48907G>A		intron_variant	Intron 2 of 9		NP_001166282.1
SLC30A8	NM_001172813.2	c.-396-6965G>A		intron_variant	Intron 1 of 10		NP_001166284.1
SLC30A8	NM_001172815.3	c.-265-39193G>A		intron_variant	Intron 1 of 10		NP_001166286.1
SLC30A8	XM_024447083.2	c.-107+48907G>A		intron_variant	Intron 1 of 8		XP_024302851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A8	ENST00000521243.5	c.-107+48907G>A		intron_variant	Intron 2 of 9	1		ENSP00000428545.1
SLC30A8	ENST00000427715.2	c.-265-39193G>A		intron_variant	Intron 1 of 10	2		ENSP00000407505.2
SLC30A8	ENST00000524274.5	c.-107+48907G>A		intron_variant	Intron 2 of 4	4		ENSP00000427760.1
SLC30A8	ENST00000521035.5	n.172-6965G>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57609 AN: 151774 Hom.: 11933 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.379 AC: 57638 AN: 151892 Hom.: 11944 Cov.: 31 AF XY: 0.380 AC XY: 28234 AN XY: 74224

African (AFR) AF: 0.212 AC: 8790 AN: 41434

American (AMR) AF: 0.504 AC: 7689 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1436 AN: 5148

South Asian (SAS) AF: 0.492 AC: 2364 AN: 4808

European-Finnish (FIN) AF: 0.350 AC: 3686 AN: 10536

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31062 AN: 67918

Other (OTH) AF: 0.405 AC: 855 AN: 2112

Alfa AF: 0.440 Hom.: 7794

Bravo AF: 0.380

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.61
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2938864; hg19: chr8-118012265;