rs2464592

Variant names:

• chr8-117171312-G-A
• rs2464592
• NM_173851.3:c.964+144G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

LOC105375716 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173851.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	NM_173851.3	MANE Select	c.964+144G>A		intron	N/A	NP_776250.2
	SLC30A8	NM_001172811.2		c.817+144G>A		intron	N/A	NP_001166282.1
	SLC30A8	NM_001172813.2		c.817+144G>A		intron	N/A	NP_001166284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.964+144G>A		intron	N/A	ENSP00000415011.2
	SLC30A8	ENST00000519688.5	TSL:1	c.817+144G>A		intron	N/A	ENSP00000431069.1
	SLC30A8	ENST00000521243.5	TSL:1	c.817+144G>A		intron	N/A	ENSP00000428545.1

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

African (AFR) AF: 0.304 AC: 5398 AN: 17778

American (AMR) AF: 0.723 AC: 23947 AN: 33108

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 11250 AN: 17498

East Asian (EAS) AF: 0.834 AC: 28765 AN: 34476

South Asian (SAS) AF: 0.679 AC: 40644 AN: 59852

European-Finnish (FIN) AF: 0.761 AC: 27777 AN: 36508

Middle Eastern (MID) AF: 0.646 AC: 1645 AN: 2548

European-Non Finnish (NFE) AF: 0.714 AC: 354957 AN: 497450

Other (OTH) AF: 0.679 AC: 24216 AN: 35686

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

African (AFR) AF: 0.302 AC: 12485 AN: 41306

American (AMR) AF: 0.683 AC: 10399 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2200 AN: 3464

East Asian (EAS) AF: 0.822 AC: 4219 AN: 5134

South Asian (SAS) AF: 0.692 AC: 3332 AN: 4812

European-Finnish (FIN) AF: 0.775 AC: 8178 AN: 10554

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.707 AC: 48021 AN: 67942

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.655 Hom.: 84718

Bravo AF: 0.580

Asia WGS AF: 0.668 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.6
DANN	Benign	0.63
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2464592; hg19: chr8-118183551; COSMIC: COSV69969297;