8-134599702-A-T

Variant names:

• chr8-134599702-A-T
• rs1036819
• NM_020863.4:c.2475+734T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020863.4(ZFAT):​c.2475+734T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 287,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 0 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]

ZFAT-AS1 (HGNC:33992): (ZFAT antisense RNA 1) This gene encodes a small antisense RNA that may be involved in regulating the sense strand locus, zinc finger and AT hook domain containing. This RNA may play a role in B cell function. A single nucleotide polymorphism in the promoter of this gene is associated with an increased risk of autoimmune thyroid disease.[provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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.2475+734T>A		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.2439+734T>A		intron	N/A	NP_001025110.2	Q9P243-2
	ZFAT	NM_001167583.3		c.2439+734T>A		intron	N/A	NP_001161055.1	Q9P243-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.2475+734T>A		intron	N/A	ENSP00000367069.3	Q9P243-1
	ZFAT	ENST00000520214.5	TSL:1	c.2439+734T>A		intron	N/A	ENSP00000428483.1	Q9P243-2
	ZFAT	ENST00000520727.5	TSL:1	c.2439+734T>A		intron	N/A	ENSP00000427831.1	Q9P243-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000697 AC: 2 AN: 287088 Hom.: 0 Cov.: 0 AF XY: 0.0000122 AC XY: 2 AN XY: 164174

African (AFR) AF: 0.00 AC: 0 AN: 7322

American (AMR) AF: 0.00 AC: 0 AN: 22026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9922

East Asian (EAS) AF: 0.00 AC: 0 AN: 9096

South Asian (SAS) AF: 0.00 AC: 0 AN: 55536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2680

European-Non Finnish (NFE) AF: 0.00000646 AC: 1 AN: 154790

Other (OTH) AF: 0.0000739 AC: 1 AN: 13538

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.7
DANN	Benign	0.87
PhyloP100		-0.20

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: rs1036819; hg19: chr8-135611945;