7-91264657-T-G

Variant names:

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

Variant summary

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

The NM_003505.2(FZD1):​c.-224T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 389,516 control chromosomes in the GnomAD database, including 72,597 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 0.64 (31457 hom., cov: 32)
  • Exomes 𝑓: 0.59 (41140 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96508 AN: 151622 Hom.: 31430 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.587 AC: 139624 AN: 237786 Hom.: 41140 Cov.: 3 AF XY: 0.585 AC XY: 70809 AN XY: 120986

African (AFR) AF: 0.765 AC: 5133 AN: 6714

American (AMR) AF: 0.613 AC: 4322 AN: 7056

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 4828 AN: 8688

East Asian (EAS) AF: 0.525 AC: 11506 AN: 21922

South Asian (SAS) AF: 0.494 AC: 1101 AN: 2230

European-Finnish (FIN) AF: 0.625 AC: 12973 AN: 20742

Middle Eastern (MID) AF: 0.508 AC: 622 AN: 1224

European-Non Finnish (NFE) AF: 0.586 AC: 90048 AN: 153588

Other (OTH) AF: 0.582 AC: 9091 AN: 15622

GnomAD4 genome AF: 0.637 AC: 96583 AN: 151730 Hom.: 31457 Cov.: 32 AF XY: 0.634 AC XY: 46991 AN XY: 74128

African (AFR) AF: 0.781 AC: 32342 AN: 41414

American (AMR) AF: 0.575 AC: 8771 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2673 AN: 5104

South Asian (SAS) AF: 0.501 AC: 2415 AN: 4824

European-Finnish (FIN) AF: 0.623 AC: 6560 AN: 10522

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.589 AC: 39921 AN: 67828

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.484 Hom.: 1295

Bravo AF: 0.642

Asia WGS AF: 0.519 AC: 1788 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		0.74
PromoterAI		0.049	Neutral
Mutation Taster		=300/0	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: rs2232157; hg19: chr7-90893972;