rs2074071

Variant names:

• chr19-57492212-G-A
• rs2074071
• NM_024691.4:c.298+1G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57492212-G-A
• chr19-57492212-G-C
• chr19-57492212-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The NM_024691.4(ZNF419):​c.298+1G>A variant causes a splice donor, intron 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, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 43 publications found

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]

ENSG00000268107 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.064579256 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 rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.298+1G>A		splice_donor_variant, intron_variant	Intron 4 of 4	ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.298+1G>A		splice_donor_variant, intron_variant	Intron 4 of 4	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+615G>A		intron_variant	Intron 2 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49587 AN: 151858 Hom.: 8206 Cov.: 29

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.: 51 AF XY: 0.296 AC XY: 215060 AN XY: 727214

African (AFR) AF: 0.399 AC: 13374 AN: 33480

American (AMR) AF: 0.274 AC: 12250 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8991 AN: 26134

East Asian (EAS) AF: 0.263 AC: 10433 AN: 39700

South Asian (SAS) AF: 0.211 AC: 18239 AN: 86256

European-Finnish (FIN) AF: 0.270 AC: 14442 AN: 53418

Middle Eastern (MID) AF: 0.339 AC: 1957 AN: 5766

European-Non Finnish (NFE) AF: 0.303 AC: 336494 AN: 1111952

Other (OTH) AF: 0.305 AC: 18396 AN: 60394

GnomAD4 genome AF: 0.327 AC: 49625 AN: 151976 Hom.: 8213 Cov.: 29 AF XY: 0.325 AC XY: 24116 AN XY: 74268

African (AFR) AF: 0.392 AC: 16220 AN: 41426

American (AMR) AF: 0.336 AC: 5122 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1405 AN: 5152

South Asian (SAS) AF: 0.194 AC: 935 AN: 4808

European-Finnish (FIN) AF: 0.271 AC: 2870 AN: 10576

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20798 AN: 67964

Other (OTH) AF: 0.354 AC: 748 AN: 2112

Alfa AF: 0.311 Hom.: 25760

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.87
CADD	Benign	16
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs2074071; hg19: chr19-58003580;