chr8-134624721-C-T

Position:

• chr8-134624721-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+12740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,096 control chromosomes in the GnomAD database, including 43,699 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 0.76 (43699 hom., cov: 32)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.448+12740G>A		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+12740G>A		intron_variant		1	NM_020863.4	ENSP00000367069	P4

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114798 AN: 151978 Hom.: 43655 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.755 AC: 114896 AN: 152096 Hom.: 43699 Cov.: 32 AF XY: 0.761 AC XY: 56609 AN XY: 74356

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.751

Alfa AF: 0.749 Hom.: 7215

Bravo AF: 0.758

Asia WGS AF: 0.811 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.51

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: rs11166629; hg19: chr8-135636964;