ENST00000502883.5:n.188+2479T>C

Variant names:

• chr4-102428583-A-G
• rs6533014
• ENST00000502883.5:n.188+2479T>C

Variant summary

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

The ENST00000502883.5(ENSG00000248161):​n.188+2479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,034 control chromosomes in the GnomAD database, including 22,426 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 0.53 (22426 hom., cov: 31)
• Consequence: ENSG00000248161 ENST00000502883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 8 publications found

Genes affected

ENSG00000248161 (HGNC:58149):

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]

SLC39A8 Gene-Disease associations (from GenCC):

• SLC39A8-CDG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKB1-AS1	NR_136202.1	n.186-8789T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000248161	ENST00000502883.5	n.188+2479T>C		intron_variant	Intron 1 of 2	5
SLC39A8	ENST00000502903.1	n.197+2479T>C		intron_variant	Intron 1 of 3	4
ENSG00000248161	ENST00000505709.1	n.221+2479T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81141 AN: 151916 Hom.: 22380 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.534 AC: 81251 AN: 152034 Hom.: 22426 Cov.: 31 AF XY: 0.532 AC XY: 39518 AN XY: 74334

African (AFR) AF: 0.667 AC: 27653 AN: 41478

American (AMR) AF: 0.468 AC: 7153 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2001 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2201 AN: 5164

South Asian (SAS) AF: 0.623 AC: 3002 AN: 4820

European-Finnish (FIN) AF: 0.411 AC: 4343 AN: 10566

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33097 AN: 67946

Other (OTH) AF: 0.539 AC: 1139 AN: 2114

Alfa AF: 0.510 Hom.: 35947

Bravo AF: 0.543

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs6533014; hg19: chr4-103349740;