chr16-68557327-A-C

Variant names:

• chr16-68557327-A-C
• rs1728785
• NM_001305203.2:c.34-671A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 86 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305203.2. 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
	ZFP90	NM_001305203.2	MANE Select	c.34-671A>C		intron	N/A	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.34-671A>C		intron	N/A	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305204.2		c.34-671A>C		intron	N/A	NP_001292133.1	Q8TF47-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP90	ENST00000563169.7	TSL:1 MANE Select	c.34-671A>C		intron	N/A	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.34-671A>C		intron	N/A	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.34-671A>C		intron	N/A	ENSP00000480309.1	Q8TF47-3

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

GnomAD2 exomes AF: 0.775 AC: 98777 AN: 127520 AF XY: 0.776

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 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

African (AFR) AF: 0.870 AC: 7442 AN: 8556

American (AMR) AF: 0.722 AC: 19637 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 8103 AN: 10724

East Asian (EAS) AF: 0.811 AC: 7386 AN: 9106

South Asian (SAS) AF: 0.770 AC: 45879 AN: 59612

European-Finnish (FIN) AF: 0.814 AC: 10031 AN: 12318

Middle Eastern (MID) AF: 0.756 AC: 2096 AN: 2772

European-Non Finnish (NFE) AF: 0.777 AC: 121118 AN: 155972

Other (OTH) AF: 0.777 AC: 10927 AN: 14056

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

African (AFR) AF: 0.873 AC: 36196 AN: 41470

American (AMR) AF: 0.745 AC: 11374 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2584 AN: 3468

East Asian (EAS) AF: 0.817 AC: 4223 AN: 5168

South Asian (SAS) AF: 0.769 AC: 3698 AN: 4810

European-Finnish (FIN) AF: 0.843 AC: 8929 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52884 AN: 68004

Other (OTH) AF: 0.775 AC: 1638 AN: 2114

Alfa AF: 0.781 Hom.: 162646

Bravo AF: 0.802

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.0
DANN	Benign	0.68
PhyloP100		0.32
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: rs1728785; hg19: chr16-68591230;