rs6577853

Positions:

• chr8-134809420-C-A
• chr8-134809420-C-G
• chr8-134809420-C-T

Variant summary

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

The XM_047422062.1(ZFAT):​c.-14208-801G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,006 control chromosomes in the GnomAD database, including 7,579 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 0.30 (7579 hom., cov: 32)
• Consequence: ZFAT XM_047422062.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

Genes affected

ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ENSG00000289405 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	XM_047422062.1	c.-14208-801G>T		intron_variant			XP_047278018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289405	ENST00000710959.1	n.28-801G>T		intron_variant
ENSG00000289405	ENST00000710960.1	n.34-801G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45902 AN: 151886 Hom.: 7570 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.302 AC: 45952 AN: 152006 Hom.: 7579 Cov.: 32 AF XY: 0.295 AC XY: 21941 AN XY: 74298

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.274

Alfa AF: 0.212 Hom.: 898

Bravo AF: 0.300

Asia WGS AF: 0.172 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6577853; hg19: chr8-135821663;