16-68557327-A-C

Position:

• chr16-68557327-A-C

Variant summary

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

The NM_001305203.2(ZFP90):​c.34-671A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 452,412 control chromosomes in the GnomAD database, including 139,911 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 0.81 (49518 hom., cov: 31)
  • Exomes 𝑓: 0.77 (90393 hom.)
• Consequence: ZFP90 NM_001305203.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP90	NM_001305203.2	c.34-671A>C		intron_variant		ENST00000563169.7	NP_001292132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP90	ENST00000563169.7	c.34-671A>C		intron_variant		1	NM_001305203.2	ENSP00000454418	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122417 AN: 151982 Hom.: 49480 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.774

GnomAD3 exomes AF: 0.775 AC: 98777 AN: 127520 Hom.: 38350 AF XY: 0.776 AC XY: 54145 AN XY: 69806

Gnomad AFR exome AF: 0.876

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.758

Gnomad EAS exome AF: 0.815

Gnomad SAS exome AF: 0.771

Gnomad FIN exome AF: 0.832

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.769

GnomAD4 exome AF: 0.775 AC: 232619 AN: 300314 Hom.: 90393 Cov.: 0 AF XY: 0.774 AC XY: 132059 AN XY: 170530

Gnomad4 AFR exome AF: 0.870

Gnomad4 AMR exome AF: 0.722

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.811

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.777

GnomAD4 genome AF: 0.805 AC: 122511 AN: 152098 Hom.: 49518 Cov.: 31 AF XY: 0.807 AC XY: 60003 AN XY: 74344

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.775

Alfa AF: 0.776 Hom.: 67576

Bravo AF: 0.802

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.0
DANN	Benign	0.68

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: rs1728785; hg19: chr16-68591230;