rs4782341

chr16-88583347-G-A

Variant summary

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

The NM_144604.4(ZC3H18):c.604-3253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,306 control chromosomes in the GnomAD database, including 59,079 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 0.88 (59079 hom., cov: 35)
• Consequence: ZC3H18 NM_144604.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

Genes affected

ZC3H18 (HGNC:25091): (zinc finger CCCH-type containing 18) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in RNA destabilization. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H18	NM_144604.4	c.604-3253G>A		intron_variant		ENST00000301011.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H18	ENST00000301011.10	c.604-3253G>A		intron_variant		1	NM_144604.4	P1
ZC3H18	ENST00000452588.6	c.604-3253G>A		intron_variant		2
ZC3H18	ENST00000569435.5	c.253-3253G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133831 AN: 152188 Hom.: 59038 Cov.: 35

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.879 AC: 133929 AN: 152306 Hom.: 59079 Cov.: 35 AF XY: 0.881 AC XY: 65605 AN XY: 74482

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.887

Alfa AF: 0.885 Hom.: 10076

Bravo AF: 0.875

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.10
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: rs4782341; hg19: chr16-88649755;