chr8-134539354-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	NM_020863.4	MANE Select	c.2977-6382A>C		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.2941-6382A>C		intron	N/A	NP_001025110.2
	ZFAT	NM_001167583.3		c.2941-6382A>C		intron	N/A	NP_001161055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.2977-6382A>C		intron	N/A	ENSP00000367069.3
	ZFAT	ENST00000520214.5	TSL:1	c.2941-6382A>C		intron	N/A	ENSP00000428483.1
	ZFAT	ENST00000520727.5	TSL:1	c.2941-6382A>C		intron	N/A	ENSP00000427831.1

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

African (AFR) AF: 0.844 AC: 35070 AN: 41542

American (AMR) AF: 0.826 AC: 12631 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4716 AN: 5174

South Asian (SAS) AF: 0.755 AC: 3638 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8052 AN: 10580

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50447 AN: 68006

Other (OTH) AF: 0.788 AC: 1663 AN: 2110

Alfa AF: 0.782 Hom.: 28937

Bravo AF: 0.793

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.91
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: rs7816909; hg19: chr8-135551597;