rs1036819

Positions:

• chr8-134599702-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020863.4(ZFAT):​c.2475+734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 439,292 control chromosomes in the GnomAD database, including 3,972 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 0.11 (1191 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2781 hom.)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.2475+734T>G		intron_variant		ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.2475+734T>G		intron_variant		1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.2439+734T>G		intron_variant		1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16667 AN: 152190 Hom.: 1186 Cov.: 33

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.127 AC: 36446 AN: 286984 Hom.: 2781 Cov.: 0 AF XY: 0.130 AC XY: 21284 AN XY: 164122

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0729

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.110 AC: 16692 AN: 152308 Hom.: 1191 Cov.: 33 AF XY: 0.111 AC XY: 8287 AN XY: 74470

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.125

Alfa AF: 0.200 Hom.: 10929

Bravo AF: 0.110

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.9
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs1036819; hg19: chr8-135611945; COSMIC: COSV64739031; COSMIC: COSV64739031;