7-91264787-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003505.2(FZD1):​c.-94C>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 0.587 in 817,494 control chromosomes in the GnomAD database, including 142,198 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 0.61 (28513 hom., cov: 33)
  • Exomes 𝑓: 0.58 (113685 hom.)
• Consequence: FZD1 NM_003505.2 5_prime_UTR
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD1	NM_003505.2	c.-94C>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.-94C>G		5_prime_UTR_variant	Exon 1 of 1	6	NM_003505.2	ENSP00000287934.2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92389 AN: 151798 Hom.: 28510 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.587

GnomAD4 exome AF: 0.583 AC: 387806 AN: 665588 Hom.: 113685 Cov.: 9 AF XY: 0.582 AC XY: 188266 AN XY: 323488

African (AFR) AF: 0.700 AC: 10497 AN: 15000

American (AMR) AF: 0.604 AC: 4716 AN: 7812

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 6324 AN: 11656

East Asian (EAS) AF: 0.525 AC: 12739 AN: 24268

South Asian (SAS) AF: 0.445 AC: 5877 AN: 13218

European-Finnish (FIN) AF: 0.610 AC: 13144 AN: 21562

Middle Eastern (MID) AF: 0.500 AC: 1049 AN: 2100

European-Non Finnish (NFE) AF: 0.586 AC: 316389 AN: 539992

Other (OTH) AF: 0.569 AC: 17071 AN: 29980

GnomAD4 genome AF: 0.608 AC: 92418 AN: 151906 Hom.: 28513 Cov.: 33 AF XY: 0.605 AC XY: 44941 AN XY: 74258

African (AFR) AF: 0.699 AC: 28993 AN: 41488

American (AMR) AF: 0.563 AC: 8599 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2672 AN: 5118

South Asian (SAS) AF: 0.459 AC: 2215 AN: 4826

European-Finnish (FIN) AF: 0.609 AC: 6441 AN: 10574

Middle Eastern (MID) AF: 0.528 AC: 152 AN: 288

European-Non Finnish (NFE) AF: 0.586 AC: 39729 AN: 67838

Other (OTH) AF: 0.580 AC: 1225 AN: 2112

Alfa AF: 0.496 Hom.: 1492

Bravo AF: 0.614

Asia WGS AF: 0.485 AC: 1669 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		0.66
PromoterAI		0.027	Neutral
Mutation Taster		=296/4	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: rs2232158; hg19: chr7-90894102;