4-141221575-A-G

Variant summary

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

The NM_014487.6(ZNF330):c.-7+467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,874 control chromosomes in the GnomAD database, including 9,252 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 (9252 hom., cov: 32)
• Consequence: ZNF330 NM_014487.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

ZNF330 (HGNC:15462): (zinc finger protein 330) Predicted to enable zinc ion binding activity. Located in chromosome, centromeric region; midbody; and nucleolus. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF330	NM_014487.6	c.-7+467A>G		intron_variant		ENST00000262990.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF330	ENST00000262990.9	c.-7+467A>G		intron_variant		1	NM_014487.6	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49598 AN: 151758 Hom.: 9243 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.327 AC: 49642 AN: 151874 Hom.: 9252 Cov.: 32 AF XY: 0.327 AC XY: 24254 AN XY: 74242

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.316

Alfa AF: 0.264 Hom.: 8679

Bravo AF: 0.342

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.7
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17007017; hg19: chr4-142142729;