rs6988616

Variant names:

• chr8-134487565-G-C
• rs6988616
• NM_020863.4:c.3493-8844C>G

Variant summary

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

The NM_020863.4(ZFAT):​c.3493-8844C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,022 control chromosomes in the GnomAD database, including 14,616 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 0.43 (14616 hom., cov: 32)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 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.3493-8844C>G		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.3457-8844C>G		intron	N/A	NP_001025110.2
	ZFAT	NM_001167583.3		c.3457-8844C>G		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.3493-8844C>G		intron	N/A	ENSP00000367069.3
	ZFAT	ENST00000520214.5	TSL:1	c.3457-8844C>G		intron	N/A	ENSP00000428483.1
	ZFAT	ENST00000520727.5	TSL:1	c.3457-8844C>G		intron	N/A	ENSP00000427831.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64887 AN: 151904 Hom.: 14611 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.427 AC: 64916 AN: 152022 Hom.: 14616 Cov.: 32 AF XY: 0.426 AC XY: 31618 AN XY: 74296

African (AFR) AF: 0.333 AC: 13781 AN: 41444

American (AMR) AF: 0.455 AC: 6960 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1673 AN: 3466

East Asian (EAS) AF: 0.0454 AC: 235 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4812

European-Finnish (FIN) AF: 0.485 AC: 5125 AN: 10568

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33703 AN: 67956

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.462 Hom.: 2088

Bravo AF: 0.417

Asia WGS AF: 0.219 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.019
DANN	Benign	0.39
PhyloP100		-1.5
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: rs6988616; hg19: chr8-135499808;