rs12680655

Positions:

• chr8-134625094-C-G
• chr8-134625094-C-T

Variant summary

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

The NM_020863.4(ZFAT):​c.448+12367G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,084 control chromosomes in the GnomAD database, including 13,622 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 0.42 (13622 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.448+12367G>C		intron_variant		ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.448+12367G>C		intron_variant		1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.412+12367G>C		intron_variant		1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63296 AN: 151966 Hom.: 13608 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.416 AC: 63339 AN: 152084 Hom.: 13622 Cov.: 33 AF XY: 0.426 AC XY: 31678 AN XY: 74342

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.414

Alfa AF: 0.380 Hom.: 6059

Bravo AF: 0.416

Asia WGS AF: 0.526 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0040
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs12680655; hg19: chr8-135637337;