rs6578234

Variant names:

• chr8-134554120-A-G
• rs6578234
• NM_020863.4:c.2976+11213T>C

Variant summary

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

The NM_020863.4(ZFAT):​c.2976+11213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,068 control chromosomes in the GnomAD database, including 10,839 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 0.37 (10839 hom., cov: 32)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.2976+11213T>C		intron_variant	Intron 11 of 15	ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.2976+11213T>C		intron_variant	Intron 11 of 15	1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.2940+11213T>C		intron_variant	Intron 11 of 15	1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56283 AN: 151950 Hom.: 10825 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.371 AC: 56345 AN: 152068 Hom.: 10839 Cov.: 32 AF XY: 0.373 AC XY: 27738 AN XY: 74316

African (AFR) AF: 0.427 AC: 17722 AN: 41474

American (AMR) AF: 0.361 AC: 5517 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3460 AN: 5160

South Asian (SAS) AF: 0.460 AC: 2213 AN: 4808

European-Finnish (FIN) AF: 0.370 AC: 3910 AN: 10576

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21614 AN: 67976

Other (OTH) AF: 0.363 AC: 766 AN: 2108

Alfa AF: 0.353 Hom.: 1654

Bravo AF: 0.371

Asia WGS AF: 0.551 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-1.6
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: rs6578234; hg19: chr8-135566363;