rs4876369

Variant names:

• chr8-117151265-A-G
• rs4876369
• NM_173851.3:c.272-1679A>G

Variant summary

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

The NM_173851.3(SLC30A8):​c.272-1679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,238 control chromosomes in the GnomAD database, including 994 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 0.10 (994 hom., cov: 32)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 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.272-1679A>G		intron	N/A	NP_776250.2
	SLC30A8	NM_001172811.2		c.125-1679A>G		intron	N/A	NP_001166282.1
	SLC30A8	NM_001172813.2		c.125-1679A>G		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.272-1679A>G		intron	N/A	ENSP00000415011.2
	SLC30A8	ENST00000519688.5	TSL:1	c.125-1679A>G		intron	N/A	ENSP00000431069.1
	SLC30A8	ENST00000521243.5	TSL:1	c.125-1679A>G		intron	N/A	ENSP00000428545.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15552 AN: 152120 Hom.: 994 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.102 AC: 15558 AN: 152238 Hom.: 994 Cov.: 32 AF XY: 0.0993 AC XY: 7388 AN XY: 74434

African (AFR) AF: 0.0321 AC: 1335 AN: 41558

American (AMR) AF: 0.101 AC: 1542 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.146 AC: 755 AN: 5168

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4818

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9810 AN: 68012

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.108 Hom.: 132

Bravo AF: 0.0983

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.44
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4876369; hg19: chr8-118163504; COSMIC: COSV69975344; COSMIC: COSV69975344;