chr7-91267516-T-C

Variant names:

• chr7-91267516-T-C
• rs3750145
• NM_003505.2:c.*692T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003505.2(FZD1):​c.*692T>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 0.153 in 167,144 control chromosomes in the GnomAD database, including 2,210 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 0.14 (1770 hom., cov: 33)
  • Exomes 𝑓: 0.24 (440 hom.)
• Consequence: FZD1 NM_003505.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD1	NM_003505.2	c.*692T>C		3_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.*692T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_003505.2	ENSP00000287934.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21904 AN: 152016 Hom.: 1768 Cov.: 33

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.244 AC: 3659 AN: 15010 Hom.: 440 Cov.: 0 AF XY: 0.244 AC XY: 1749 AN XY: 7160

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.100 AC: 1 AN: 10

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.245 AC: 3597 AN: 14668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.170 AC: 38 AN: 224

Other (OTH) AF: 0.240 AC: 23 AN: 96

GnomAD4 genome AF: 0.144 AC: 21906 AN: 152134 Hom.: 1770 Cov.: 33 AF XY: 0.147 AC XY: 10914 AN XY: 74402

African (AFR) AF: 0.0823 AC: 3417 AN: 41534

American (AMR) AF: 0.131 AC: 2004 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1055 AN: 5158

South Asian (SAS) AF: 0.151 AC: 727 AN: 4818

European-Finnish (FIN) AF: 0.238 AC: 2515 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11000 AN: 67980

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.151 Hom.: 792

Bravo AF: 0.134

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.80
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: rs3750145; hg19: chr7-90896831; COSMIC: COSV55310597;