NM_181710.4:c.*138A>C

Variant names:

• chr19-5456919-A-C
• rs2240747
• NM_181710.4:c.*138A>C

Variant summary

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

The NM_181710.4(ZNRF4):​c.*138A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 950,814 control chromosomes in the GnomAD database, including 17,466 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 0.17 (2616 hom., cov: 32)
  • Exomes 𝑓: 0.18 (14850 hom.)
• Consequence: ZNRF4 NM_181710.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181710.4. 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.*138A>C		downstream_gene	N/A	NP_859061.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRF4	ENST00000222033.6	TSL:6 MANE Select	c.*138A>C		downstream_gene	N/A	ENSP00000222033.4	Q8WWF5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26143 AN: 151970 Hom.: 2617 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.184 AC: 147357 AN: 798726 Hom.: 14850 AF XY: 0.185 AC XY: 73182 AN XY: 396214

African (AFR) AF: 0.102 AC: 1924 AN: 18876

American (AMR) AF: 0.181 AC: 3117 AN: 17176

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 3414 AN: 15422

East Asian (EAS) AF: 0.393 AC: 12447 AN: 31642

South Asian (SAS) AF: 0.207 AC: 9259 AN: 44646

European-Finnish (FIN) AF: 0.238 AC: 10201 AN: 42944

Middle Eastern (MID) AF: 0.148 AC: 404 AN: 2730

European-Non Finnish (NFE) AF: 0.169 AC: 99701 AN: 588398

Other (OTH) AF: 0.187 AC: 6890 AN: 36892

GnomAD4 genome AF: 0.172 AC: 26161 AN: 152088 Hom.: 2616 Cov.: 32 AF XY: 0.180 AC XY: 13345 AN XY: 74344

African (AFR) AF: 0.103 AC: 4291 AN: 41528

American (AMR) AF: 0.189 AC: 2883 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1962 AN: 5130

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2693 AN: 10590

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11854 AN: 67964

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.173 Hom.: 3931

Bravo AF: 0.168

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.48
PhyloP100		0.031
Mutation Taster		=95/5	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2240747; hg19: chr19-5456930; COSMIC: COSV55774076;