NM_003505.2:c.-225C>T

Variant names:

• chr7-91264656-C-T
• rs2232156
• NM_003505.2:c.-225C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003505.2(FZD1):​c.-225C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 390,170 control chromosomes in the GnomAD database, including 7 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 0.0042 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: FZD1 NM_003505.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS2: High AC in GnomAd4 at 642 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD1	NM_003505.2	c.-225C>T		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.-225C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_003505.2	ENSP00000287934.2

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 643 AN: 151934 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

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: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000605 AC: 144 AN: 238128 Hom.: 2 Cov.: 2 AF XY: 0.000454 AC XY: 55 AN XY: 121152

African (AFR) AF: 0.0145 AC: 97 AN: 6708

American (AMR) AF: 0.00199 AC: 14 AN: 7052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8714

East Asian (EAS) AF: 0.00 AC: 0 AN: 21924

South Asian (SAS) AF: 0.00 AC: 0 AN: 2248

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1238

European-Non Finnish (NFE) AF: 0.0000195 AC: 3 AN: 153818

Other (OTH) AF: 0.00191 AC: 30 AN: 15670

GnomAD4 genome AF: 0.00422 AC: 642 AN: 152042 Hom.: 5 Cov.: 33 AF XY: 0.00421 AC XY: 313 AN XY: 74338

African (AFR) AF: 0.0138 AC: 573 AN: 41490

American (AMR) AF: 0.00393 AC: 60 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67942

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.0000697 Hom.: 0

Bravo AF: 0.00485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		-0.23
PromoterAI		-0.020	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: rs2232156; hg19: chr7-90893971;