8-134586977-G-A

Variant names:

• chr8-134586977-G-A
• rs11778878
• NM_020863.4:c.2713+1269C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020863.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	NM_020863.4	MANE Select	c.2713+1269C>T		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.2677+1269C>T		intron	N/A	NP_001025110.2
	ZFAT	NM_001167583.3		c.2677+1269C>T		intron	N/A	NP_001161055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.2713+1269C>T		intron	N/A	ENSP00000367069.3
	ZFAT	ENST00000520214.5	TSL:1	c.2677+1269C>T		intron	N/A	ENSP00000428483.1
	ZFAT	ENST00000520727.5	TSL:1	c.2677+1269C>T		intron	N/A	ENSP00000427831.1

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

African (AFR) AF: 0.137 AC: 5696 AN: 41514

American (AMR) AF: 0.192 AC: 2931 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3470

East Asian (EAS) AF: 0.0874 AC: 453 AN: 5184

South Asian (SAS) AF: 0.229 AC: 1100 AN: 4812

European-Finnish (FIN) AF: 0.277 AC: 2931 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20326 AN: 67982

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.226 Hom.: 1732

Bravo AF: 0.223

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.16
DANN	Benign	0.39
PhyloP100		-1.7
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: rs11778878; hg19: chr8-135599220;