rs713065

Variant names:

• chr11-86946478-A-G
• rs713065
• NM_012193.4:c.*4664T>C

Variant summary

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

The NM_012193.4(FZD4):​c.*4664T>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 0.567 in 152,044 control chromosomes in the GnomAD database, including 24,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24796 hom., cov: 32)
  • Exomes 𝑓: 0.53 (7 hom.)
• Consequence: FZD4 NM_012193.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.286
• Publications: 21 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=-0.81).
• BP6: Variant 11-86946478-A-G is Benign according to our data. Variant chr11-86946478-A-G is described in ClinVar as Benign. ClinVar VariationId is 306335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012193.4. 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
	FZD4	NM_012193.4	MANE Select	c.*4664T>C		3_prime_UTR	Exon 2 of 2	NP_036325.2
	PRSS23	NR_120591.3		n.435-3878A>G		intron	N/A
	PRSS23	NR_120592.2		n.328-4738A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD4	ENST00000531380.2	TSL:1 MANE Select	c.*4664T>C		3_prime_UTR	Exon 2 of 2	ENSP00000434034.1
	PRSS23	ENST00000532234.5	TSL:1	n.*65-3878A>G		intron	N/A	ENSP00000436676.1
	PRSS23	ENST00000533902.2	TSL:4	c.207-4738A>G		intron	N/A	ENSP00000437268.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86079 AN: 151870 Hom.: 24795 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.534 AC: 31 AN: 58 Hom.: 7 Cov.: 0 AF XY: 0.536 AC XY: 15 AN XY: 28

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.625 AC: 5 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.525 AC: 21 AN: 40

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

GnomAD4 genome AF: 0.567 AC: 86102 AN: 151986 Hom.: 24796 Cov.: 32 AF XY: 0.562 AC XY: 41773 AN XY: 74300

African (AFR) AF: 0.466 AC: 19313 AN: 41448

American (AMR) AF: 0.578 AC: 8833 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2270 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2245 AN: 5156

South Asian (SAS) AF: 0.498 AC: 2400 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6000 AN: 10534

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42889 AN: 67960

Other (OTH) AF: 0.598 AC: 1264 AN: 2112

Alfa AF: 0.616 Hom.: 84507

Bravo AF: 0.565

Asia WGS AF: 0.469 AC: 1632 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	-0.81
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs713065; hg19: chr11-86657520;