19-5455252-A-G

Variant names:

• chr19-5455252-A-G
• rs1564759
• NM_181710.4:c.-240A>G

Variant summary

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

The NM_181710.4(ZNRF4):​c.-240A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,942 control chromosomes in the GnomAD database, including 18,172 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 0.48 (18172 hom., cov: 32)
• Consequence: ZNRF4 NM_181710.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

Genes affected

ZNRF4 (HGNC:17726): (zinc and ring finger 4) Predicted to enable ubiquitin protein ligase activity. Involved in ubiquitin-dependent protein catabolic process. Located in endoplasmic reticulum membrane. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNRF4	NM_181710.4	c.-240A>G		upstream_gene_variant		ENST00000222033.6	NP_859061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRF4	ENST00000222033.6	c.-240A>G		upstream_gene_variant		6	NM_181710.4	ENSP00000222033.4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72693 AN: 151824 Hom.: 18147 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.479 AC: 72767 AN: 151942 Hom.: 18172 Cov.: 32 AF XY: 0.486 AC XY: 36106 AN XY: 74242

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.484

Alfa AF: 0.496 Hom.: 12988

Bravo AF: 0.474

Asia WGS AF: 0.716 AC: 2486 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	0.96
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1564759; hg19: chr19-5455263;