rs733254

Variant names:

• chr8-134626389-C-A
• rs733254
• NM_020863.4:c.448+11072G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-134626389-C-A
• chr8-134626389-C-G
• chr8-134626389-C-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.448+11072G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,124 control chromosomes in the GnomAD database, including 7,097 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 0.30 (7097 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 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.448+11072G>T		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.412+11072G>T		intron	N/A	NP_001025110.2	Q9P243-2
	ZFAT	NM_001167583.3		c.412+11072G>T		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.448+11072G>T		intron	N/A	ENSP00000367069.3	Q9P243-1
	ZFAT	ENST00000520214.5	TSL:1	c.412+11072G>T		intron	N/A	ENSP00000428483.1	Q9P243-2
	ZFAT	ENST00000520727.5	TSL:1	c.412+11072G>T		intron	N/A	ENSP00000427831.1	Q9P243-2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45475 AN: 152006 Hom.: 7086 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.299 AC: 45512 AN: 152124 Hom.: 7097 Cov.: 33 AF XY: 0.307 AC XY: 22860 AN XY: 74356

African (AFR) AF: 0.275 AC: 11393 AN: 41496

American (AMR) AF: 0.340 AC: 5190 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3464

East Asian (EAS) AF: 0.535 AC: 2766 AN: 5166

South Asian (SAS) AF: 0.453 AC: 2186 AN: 4826

European-Finnish (FIN) AF: 0.376 AC: 3976 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18423 AN: 67988

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.280 Hom.: 18400

Bravo AF: 0.294

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-0.24
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: rs733254; hg19: chr8-135638632;