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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.20-6911C>T		intron_variant	Intron 1 of 15	ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.20-6911C>T		intron_variant	Intron 1 of 15	1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.-17-6911C>T		intron_variant	Intron 1 of 15	1		ENSP00000394501.2

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 v4.3

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;