rs10898563

Variant names:

• chr11-86948171-A-G
• rs10898563
• NM_012193.4:c.*2971T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000531380.2(FZD4):​c.*2971T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,960 control chromosomes in the GnomAD database, including 7,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7129 hom., cov: 31)
  • Exomes 𝑓: 0.39 (5 hom.)
• Consequence: FZD4 ENST00000531380.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.417
• Publications: 28 publications found

Genes affected

FZD4 (HGNC:4042): (frizzled class receptor 4) This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]

PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-86948171-A-G is Benign according to our data. Variant chr11-86948171-A-G is described in ClinVar as Benign. ClinVar VariationId is 306365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000531380.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD4	NM_012193.4	MANE Select	c.*2971T>C		3_prime_UTR	Exon 2 of 2	NP_036325.2
	PRSS23	NR_120591.3		n.435-2185A>G		intron	N/A
	PRSS23	NR_120592.2		n.328-3045A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD4	ENST00000531380.2	TSL:1 MANE Select	c.*2971T>C		3_prime_UTR	Exon 2 of 2	ENSP00000434034.1
	PRSS23	ENST00000532234.5	TSL:1	n.*65-2185A>G		intron	N/A	ENSP00000436676.1
	PRSS23	ENST00000533902.2	TSL:4	c.207-3045A>G		intron	N/A	ENSP00000437268.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41857 AN: 151780 Hom.: 7128 Cov.: 31

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.387 AC: 24 AN: 62 Hom.: 5 Cov.: 0 AF XY: 0.450 AC XY: 18 AN XY: 40

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.348 AC: 16 AN: 46

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.275 AC: 41847 AN: 151898 Hom.: 7129 Cov.: 31 AF XY: 0.272 AC XY: 20208 AN XY: 74210

African (AFR) AF: 0.0929 AC: 3848 AN: 41410

American (AMR) AF: 0.269 AC: 4111 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3468

East Asian (EAS) AF: 0.0944 AC: 487 AN: 5160

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4814

European-Finnish (FIN) AF: 0.360 AC: 3799 AN: 10556

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25838 AN: 67918

Other (OTH) AF: 0.308 AC: 648 AN: 2106

Alfa AF: 0.344 Hom.: 24621

Bravo AF: 0.263

Asia WGS AF: 0.124 AC: 435 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Exudative vitreoretinopathy 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10898563; hg19: chr11-86659213;