chr14-28766942-C-CG

Position:

• chr14-28766942-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005249.5(FOXG1):​c.-329dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (0 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.926

Genes affected

FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]

LINC01551 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-28766942-C-CG is Benign according to our data. Variant chr14-28766942-C-CG is described in ClinVar as [Likely_benign]. Clinvar id is 1207223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00346 (494/142862) while in subpopulation AFR AF= 0.0107 (431/40266). AF 95% confidence interval is 0.00987. There are 5 homozygotes in gnomad4. There are 246 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 494 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.-329dupG		5_prime_UTR_variant	1/1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071	c.-329dupG		5_prime_UTR_variant	1/1		NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482	c.-329dupG		5_prime_UTR_variant	2/2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+938dupG		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 494 AN: 142768 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00122

Gnomad ASJ AF: 0.00122

Gnomad EAS AF: 0.00179

Gnomad SAS AF: 0.000443

Gnomad FIN AF: 0.000109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000410

Gnomad OTH AF: 0.00207

GnomAD4 exome AF: 0.00243 AC: 2 AN: 822 Hom.: 0 Cov.: 0 AF XY: 0.00161 AC XY: 1 AN XY: 620

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00313

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00346 AC: 494 AN: 142862 Hom.: 5 Cov.: 0 AF XY: 0.00354 AC XY: 246 AN XY: 69516

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.00122

Gnomad4 ASJ AF: 0.00122

Gnomad4 EAS AF: 0.00180

Gnomad4 SAS AF: 0.000444

Gnomad4 FIN AF: 0.000109

Gnomad4 NFE AF: 0.000410

Gnomad4 OTH AF: 0.00205

Alfa AF: 0.0849 Hom.: 11

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555321095; hg19: chr14-29236148;