8-134769539-T-G

Variant names:

• chr8-134769539-T-G
• rs11776156
• ENST00000688995.2:n.143-6887A>C

Variant summary

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

The ENST00000688995.2(ENSG00000289405):​n.143-6887A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,094 control chromosomes in the GnomAD database, including 45,074 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 0.77 (45074 hom., cov: 32)
• Consequence: ENSG00000289405 ENST00000688995.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 3 publications found

Genes affected

ENSG00000289405 (HGNC:):

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	XM_047422062.1	c.-4754-6887A>C		intron_variant	Intron 2 of 18		XP_047278018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289405	ENST00000688995.2	n.143-6887A>C		intron_variant	Intron 1 of 2
ENSG00000289405	ENST00000773977.1	n.116-6887A>C		intron_variant	Intron 1 of 2
ENSG00000289405	ENST00000773978.1	n.115-6887A>C		intron_variant	Intron 1 of 2
ENSG00000289405	ENST00000773979.1	n.439-6887A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116292 AN: 151976 Hom.: 45014 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.765 AC: 116412 AN: 152094 Hom.: 45074 Cov.: 32 AF XY: 0.766 AC XY: 56955 AN XY: 74348

African (AFR) AF: 0.887 AC: 36829 AN: 41520

American (AMR) AF: 0.768 AC: 11732 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3216 AN: 5150

South Asian (SAS) AF: 0.757 AC: 3653 AN: 4826

European-Finnish (FIN) AF: 0.743 AC: 7855 AN: 10572

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48125 AN: 67962

Other (OTH) AF: 0.760 AC: 1604 AN: 2110

Alfa AF: 0.748 Hom.: 7463

Bravo AF: 0.767

Asia WGS AF: 0.731 AC: 2542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11776156; hg19: chr8-135781782;