Variant rs2074071 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_024691.4(ZNF419):c.298+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,800 control chromosomes in the GnomAD database, including 73,855 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 ( 8213 hom., cov: 29)

Exomes 𝑓: 0.30 ( 65642 hom. )

Consequence

ZNF419
NM_024691.4 splice_donor

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF419 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06392694 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.3, offset of 7, new splice context is: ttgGTgggt. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF419	NM_024691.4 linkuse as main transcript	c.298+1G>A		splice_donor_variant		ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12 linkuse as main transcript	c.298+1G>A		splice_donor_variant		1	NM_024691.4	ENSP00000221735	A2	Q96HQ0-1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49587

AN:

151858

Hom.:

8206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.297

AC:

434576

AN:

1461824

Hom.:

65642

Cov.:

AF XY:

0.296

AC XY:

215060

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.399

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.327

AC:

49625

AN:

151976

Hom.:

8213

Cov.:

AF XY:

0.325

AC XY:

24116

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.392

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.310

Hom.:

18282

Bravo

AF:

0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over