NM_003505.2:c.-224T>A

Variant names:

• chr7-91264657-T-A
• rs2232157
• NM_003505.2:c.-224T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003505.2(FZD1):​c.-224T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,676 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FZD1 NM_003505.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD1	NM_003505.2	c.-224T>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000287934.4	NP_003496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD1	ENST00000287934.4	c.-224T>A		5_prime_UTR_variant	Exon 1 of 1	6	NM_003505.2	ENSP00000287934.2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151676 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 238006 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 121106

African (AFR) AF: 0.00 AC: 0 AN: 6716

American (AMR) AF: 0.00 AC: 0 AN: 7062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8696

East Asian (EAS) AF: 0.00 AC: 0 AN: 21934

South Asian (SAS) AF: 0.00 AC: 0 AN: 2230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 153744

Other (OTH) AF: 0.00 AC: 0 AN: 15640

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151676 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74044

African (AFR) AF: 0.0000242 AC: 1 AN: 41308

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67850

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 1295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		0.74
PromoterAI		-0.0030	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: rs2232157; hg19: chr7-90893972;