rs1159788

Positions:

• chr4-102386392-A-C

Variant summary

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

The ENST00000502903.1(SLC39A8):​n.198-882T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,960 control chromosomes in the GnomAD database, including 25,699 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 0.56 (25699 hom., cov: 31)
• Consequence: SLC39A8 ENST00000502903.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

SLC39A8 (HGNC:20862): (solute carrier family 39 member 8) This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke. Multiple transcript variants encoding different isoforms have been found for this gene. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000502903.1	n.198-882T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84929 AN: 151842 Hom.: 25684 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.559 AC: 84967 AN: 151960 Hom.: 25699 Cov.: 31 AF XY: 0.558 AC XY: 41436 AN XY: 74292

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.606

Alfa AF: 0.608 Hom.: 4955

Bravo AF: 0.543

Asia WGS AF: 0.473 AC: 1644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.64
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1159788; hg19: chr4-103307549;