14-28767055-CT-C

Position:

• chr14-28767055-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005249.5(FOXG1):​c.-210del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 143,078 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (18 hom., cov: 29)
  • Exomes 𝑓: 0.068 (0 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

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:19828): (long intergenic non-protein coding RNA 1551)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-28767055-CT-C is Benign according to our data. Variant chr14-28767055-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1188300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.-210del		5_prime_UTR_variant	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.-210del		5_prime_UTR_variant	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.-210del		5_prime_UTR_variant	2/2			P1
LINC01551	ENST00000675861.1	n.374+1057del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1524 AN: 139646 Hom.: 18 Cov.: 29

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00626

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.00165

Gnomad SAS AF: 0.000905

Gnomad FIN AF: 0.000130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0685 AC: 235 AN: 3432 Hom.: 0 Cov.: 0 AF XY: 0.0759 AC XY: 149 AN XY: 1962

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0626

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0109 AC: 1522 AN: 139646 Hom.: 18 Cov.: 29 AF XY: 0.0107 AC XY: 726 AN XY: 67582

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.00625

Gnomad4 ASJ AF: 0.000304

Gnomad4 EAS AF: 0.00165

Gnomad4 SAS AF: 0.000911

Gnomad4 FIN AF: 0.000130

Gnomad4 NFE AF: 0.00170

Gnomad4 OTH AF: 0.0105

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

Aug 21, 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: rs542787885; hg19: chr14-29236261;