16-68566448-C-T

Variant names:

• chr16-68566448-C-T
• rs17689437
• ENST00000564558.5:n.*3576C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000564558.5(ZFP90):​n.*3576C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 985,408 control chromosomes in the GnomAD database, including 10,319 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 0.13 (1435 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8884 hom.)
• Consequence: ZFP90 ENST00000564558.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 22 publications found

Genes affected

ZFP90 (HGNC:23329): (ZFP90 zinc finger protein) This gene encodes a member of the zinc finger protein family that modulates gene expression. The encoded protein derepresses the transcription of certain fetal cardiac genes and may contribute to the genetic reprogramming that occurs during the development of heart failure. Genome wide association studies have identified this gene among ulcerative colitis risk loci. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP90	NM_001305203.2	c.*1750C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000563169.7	NP_001292132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP90	ENST00000563169.7	c.*1750C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001305203.2	ENSP00000454418.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19920 AN: 152042 Hom.: 1435 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.144 AC: 120195 AN: 833246 Hom.: 8884 Cov.: 36 AF XY: 0.144 AC XY: 55566 AN XY: 384790

African (AFR) AF: 0.114 AC: 1806 AN: 15786

American (AMR) AF: 0.0986 AC: 97 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 855 AN: 5152

East Asian (EAS) AF: 0.00743 AC: 28 AN: 3770

South Asian (SAS) AF: 0.0537 AC: 884 AN: 16460

European-Finnish (FIN) AF: 0.162 AC: 45 AN: 278

Middle Eastern (MID) AF: 0.110 AC: 178 AN: 1620

European-Non Finnish (NFE) AF: 0.148 AC: 112824 AN: 761898

Other (OTH) AF: 0.127 AC: 3478 AN: 27298

GnomAD4 genome AF: 0.131 AC: 19924 AN: 152162 Hom.: 1435 Cov.: 32 AF XY: 0.130 AC XY: 9635 AN XY: 74384

African (AFR) AF: 0.111 AC: 4603 AN: 41528

American (AMR) AF: 0.113 AC: 1735 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4822

European-Finnish (FIN) AF: 0.193 AC: 2036 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10363 AN: 67982

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.140 Hom.: 4561

Bravo AF: 0.125

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.54
PhyloP100		-0.065
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: rs17689437; hg19: chr16-68600351;