rs1443753

chr7-122309264-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_036484.1(FEZF1-AS1):n.2160-320T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,112 control chromosomes in the GnomAD database, including 24,858 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 0.56 (24858 hom., cov: 33)
• Consequence: FEZF1-AS1 NR_036484.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

Genes affected

FEZF1-AS1 (HGNC:41001): (FEZF1 antisense RNA 1)

FEZF1 (HGNC:22788): (FEZ family zinc finger 1) This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEZF1-AS1	NR_036484.1	n.2160-320T>C		intron_variant, non_coding_transcript_variant
FEZF1	XM_005250337.4	c.-75+921A>G		intron_variant
FEZF1	XM_011516202.3	c.-75+921A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZF1-AS1	ENST00000428449.5	n.2160-320T>C		intron_variant, non_coding_transcript_variant		2
FEZF1	ENST00000418046.1	c.-75+921A>G		intron_variant		2
FEZF1-AS1	ENST00000653165.1	n.351-320T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85314 AN: 151994 Hom.: 24847 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.561 AC: 85359 AN: 152112 Hom.: 24858 Cov.: 33 AF XY: 0.564 AC XY: 41935 AN XY: 74354

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.544

Alfa AF: 0.607 Hom.: 31796

Bravo AF: 0.541

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.81
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1443753; hg19: chr7-121949318;