8-134539354-T-G

Variant names:

• chr8-134539354-T-G
• rs7816909
• NM_020863.4:c.2977-6382A>C

Variant summary

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

The NM_020863.4(ZFAT):​c.2977-6382A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,200 control chromosomes in the GnomAD database, including 47,099 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 0.78 (47099 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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 rank	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.2977-6382A>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.2977-6382A>C		intron_variant	Intron 11 of 15	1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.2941-6382A>C		intron_variant	Intron 11 of 15	1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119191 AN: 152082 Hom.: 47053 Cov.: 33

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.784 AC: 119295 AN: 152200 Hom.: 47099 Cov.: 33 AF XY: 0.784 AC XY: 58340 AN XY: 74394

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.788

Alfa AF: 0.766 Hom.: 12841

Bravo AF: 0.793

Asia WGS AF: 0.816 AC: 2836 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	2.4
DANN	Benign	0.63

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: rs7816909; hg19: chr8-135551597;