19-5455252-A-G

Variant names:

• chr19-5455252-A-G
• rs1564759
• ENST00000752382.1:n.84T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000752382.1(ENSG00000297997):​n.84T>C variant causes a non coding transcript exon 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: ENSG00000297997 ENST00000752382.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 1 publications found

Genes affected

ENSG00000297997 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000752382.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRF4	NM_181710.4	MANE Select	c.-240A>G		upstream_gene	N/A	NP_859061.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000297997	ENST00000752382.1		n.84T>C		non_coding_transcript_exon	Exon 1 of 2
	ZNRF4	ENST00000222033.6	TSL:6 MANE Select	c.-240A>G		upstream_gene	N/A	ENSP00000222033.4	Q8WWF5

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

African (AFR) AF: 0.361 AC: 14941 AN: 41442

American (AMR) AF: 0.505 AC: 7709 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3892 AN: 5156

South Asian (SAS) AF: 0.620 AC: 2992 AN: 4822

European-Finnish (FIN) AF: 0.530 AC: 5594 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33920 AN: 67928

Other (OTH) AF: 0.484 AC: 1021 AN: 2108

Alfa AF: 0.494 Hom.: 15396

Bravo AF: 0.474

Asia WGS AF: 0.716 AC: 2486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.96
DANN	Benign	0.73
PhyloP100		-0.29
PromoterAI		0.0059	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1564759;

hg19: chr19-5455263;