rs4743034

Positions:

• chr9-106870072-G-A

Variant summary

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

The NM_021224.6(ZNF462):​c.-31+6717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,078 control chromosomes in the GnomAD database, including 6,307 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 0.27 (6307 hom., cov: 32)
• Consequence: ZNF462 NM_021224.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

Genes affected

ZNF462 (HGNC:21684): (zinc finger protein 462) The protein encoded by this gene belongs to C2H2-type zinc finger family of proteins. It contains multiple C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF462	NM_021224.6	c.-31+6717G>A		intron_variant		ENST00000277225.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF462	ENST00000277225.10	c.-31+6717G>A		intron_variant		1	NM_021224.6	P1
ZNF462	ENST00000472574.1	c.-31+6717G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41293 AN: 151958 Hom.: 6281 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.272 AC: 41354 AN: 152078 Hom.: 6307 Cov.: 32 AF XY: 0.270 AC XY: 20038 AN XY: 74338

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.258

Alfa AF: 0.230 Hom.: 9244

Bravo AF: 0.275

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.50

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: rs4743034; hg19: chr9-109632353;