NM_003505.2:c.-94C>T

Variant names:

• chr7-91264787-C-T
• rs2232158
• NM_003505.2:c.-94C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003505.2(FZD1):​c.-94C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 667,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: FZD1 NM_003505.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660
• Publications: 17 publications found

Genes affected

FZD1 (HGNC:4038): (frizzled class receptor 1) Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD1 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, 7 transmembrane domains, and a C-terminal PDZ domain-binding motif. The FZD1 transcript is expressed in various tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003505.2. 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
	FZD1	NM_003505.2	MANE Select	c.-94C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_003496.1
	FZD1	NM_003505.2	MANE Select	c.-94C>T		5_prime_UTR	Exon 1 of 1	NP_003496.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD1	ENST00000287934.4	TSL:6 MANE Select	c.-94C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000287934.2
	FZD1	ENST00000287934.4	TSL:6 MANE Select	c.-94C>T		5_prime_UTR	Exon 1 of 1	ENSP00000287934.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000300 AC: 2 AN: 667386 Hom.: 0 Cov.: 9 AF XY: 0.00000308 AC XY: 1 AN XY: 324356

African (AFR) AF: 0.00 AC: 0 AN: 15024

American (AMR) AF: 0.00 AC: 0 AN: 7818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11670

East Asian (EAS) AF: 0.00 AC: 0 AN: 24288

South Asian (SAS) AF: 0.00 AC: 0 AN: 13264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2104

European-Non Finnish (NFE) AF: 0.00000369 AC: 2 AN: 541624

Other (OTH) AF: 0.00 AC: 0 AN: 30026

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		0.66
PromoterAI		-0.067	Neutral

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: rs2232158; hg19: chr7-90894102;