rs16905215

Variant names:

• chr8-134664648-G-A
• rs16905215
• NM_020863.4:c.20-6911C>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.20-6911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,124 control chromosomes in the GnomAD database, including 8,948 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 0.33 (8948 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.41 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.20-6911C>T		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.-17-6911C>T		intron	N/A	NP_001025110.2	Q9P243-2
	ZFAT	NM_001167583.3		c.-17-6911C>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.20-6911C>T		intron	N/A	ENSP00000367069.3	Q9P243-1
	ZFAT	ENST00000520214.5	TSL:1	c.-17-6911C>T		intron	N/A	ENSP00000428483.1	Q9P243-2
	ZFAT	ENST00000520727.5	TSL:1	c.-17-6911C>T		intron	N/A	ENSP00000427831.1	Q9P243-2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50541 AN: 152006 Hom.: 8938 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.332 AC: 50578 AN: 152124 Hom.: 8948 Cov.: 33 AF XY: 0.334 AC XY: 24811 AN XY: 74364

African (AFR) AF: 0.221 AC: 9166 AN: 41518

American (AMR) AF: 0.376 AC: 5742 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1562 AN: 5162

South Asian (SAS) AF: 0.426 AC: 2051 AN: 4818

European-Finnish (FIN) AF: 0.355 AC: 3750 AN: 10570

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25758 AN: 67980

Other (OTH) AF: 0.332 AC: 701 AN: 2114

Alfa AF: 0.363 Hom.: 17549

Bravo AF: 0.326

Asia WGS AF: 0.354 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.59
PhyloP100		-1.4
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: rs16905215; hg19: chr8-135676891;