4-141221575-A-G

Variant names:

• chr4-141221575-A-G
• rs17007017
• NM_014487.6:c.-7+467A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014487.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF330	NM_014487.6	MANE Select	c.-7+467A>G		intron	N/A	NP_055302.1
	ZNF330	NM_001292002.2		c.-116+467A>G		intron	N/A	NP_001278931.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF330	ENST00000262990.9	TSL:1 MANE Select	c.-7+467A>G		intron	N/A	ENSP00000262990.4
	ZNF330	ENST00000512809.5	TSL:3	c.-7+521A>G		intron	N/A	ENSP00000422599.1
	ZNF330	ENST00000512738.5	TSL:4	c.-7+559A>G		intron	N/A	ENSP00000422251.1

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

African (AFR) AF: 0.480 AC: 19864 AN: 41392

American (AMR) AF: 0.276 AC: 4208 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3164 AN: 5146

South Asian (SAS) AF: 0.312 AC: 1497 AN: 4804

European-Finnish (FIN) AF: 0.207 AC: 2183 AN: 10548

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16598 AN: 67940

Other (OTH) AF: 0.316 AC: 666 AN: 2106

Alfa AF: 0.281 Hom.: 15825

Bravo AF: 0.342

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17007017; hg19: chr4-142142729;