chr3-62374696-T-C

Variant names:

• chr3-62374696-T-C
• rs3755827
• XR_940901.2:n.300-186A>G

Variant summary

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

The XR_940901.2(LOC105377647):​n.300-186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,148 control chromosomes in the GnomAD database, including 4,631 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 0.22 (4631 hom., cov: 33)
• Consequence: LOC105377647 XR_940901.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 5 publications found

Genes affected

LOC105377647 (HGNC:):

FEZF2 (HGNC:13506): (FEZ family zinc finger 2) Predicted to enable transcription cis-regulatory region binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including negative regulation of transcription by RNA polymerase II; nervous system development; and regulation of neuron differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FEZF2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000951993.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEZF2	ENST00000951993.1		c.-716A>G		upstream_gene	N/A	ENSP00000622052.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32835 AN: 152030 Hom.: 4605 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32900 AN: 152148 Hom.: 4631 Cov.: 33 AF XY: 0.216 AC XY: 16055 AN XY: 74384

African (AFR) AF: 0.402 AC: 16695 AN: 41482

American (AMR) AF: 0.169 AC: 2592 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5174

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4824

European-Finnish (FIN) AF: 0.141 AC: 1497 AN: 10588

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8297 AN: 67990

Other (OTH) AF: 0.212 AC: 448 AN: 2116

Alfa AF: 0.153 Hom.: 1700

Bravo AF: 0.223

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		0.30
PromoterAI		0.0080	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3755827; hg19: chr3-62360371;