rs11778878

chr8-134586977-G-Achr8-134586977-G-Cchr8-134586977-G-T

Variant summary

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

The NM_020863.4(ZFAT):c.2713+1269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,152 control chromosomes in the GnomAD database, including 4,788 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 0.24 (4788 hom., cov: 32)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAT	NM_020863.4	c.2713+1269C>T		intron_variant		ENST00000377838.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAT	ENST00000377838.8	c.2713+1269C>T		intron_variant		1	NM_020863.4	P4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35756 AN: 152034 Hom.: 4786 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.235 AC: 35767 AN: 152152 Hom.: 4788 Cov.: 32 AF XY: 0.233 AC XY: 17312 AN XY: 74362

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.0874

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.234

Alfa AF: 0.219 Hom.: 1307

Bravo AF: 0.223

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.16
Dann	Benign	0.39

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: rs11778878; hg19: chr8-135599220;