8-134666561-C-T

Variant names:

• chr8-134666561-C-T
• rs9785140
• NM_020863.4:c.20-8824G>A

Variant summary

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

The NM_020863.4(ZFAT):​c.20-8824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,960 control chromosomes in the GnomAD database, including 9,451 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 0.35 (9451 hom., cov: 32)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.20-8824G>A		intron_variant	Intron 1 of 15	ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.20-8824G>A		intron_variant	Intron 1 of 15	1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.-17-8824G>A		intron_variant	Intron 1 of 15	1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52525 AN: 151842 Hom.: 9443 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.346 AC: 52563 AN: 151960 Hom.: 9451 Cov.: 32 AF XY: 0.347 AC XY: 25773 AN XY: 74270

African (AFR) AF: 0.268 AC: 11092 AN: 41432

American (AMR) AF: 0.380 AC: 5812 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1405 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5158

South Asian (SAS) AF: 0.427 AC: 2053 AN: 4812

European-Finnish (FIN) AF: 0.355 AC: 3741 AN: 10540

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25764 AN: 67956

Other (OTH) AF: 0.338 AC: 715 AN: 2114

Alfa AF: 0.364 Hom.: 43382

Bravo AF: 0.341

Asia WGS AF: 0.356 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.25
PhyloP100		0.73
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: rs9785140; hg19: chr8-135678804;