14-28767485-CGCA-C

Position:

• chr14-28767485-CGCA-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005249.5(FOXG1):​c.218_220del​(p.Gln73del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,054,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P69P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: FOXG1 NM_005249.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.869

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-28767485-CGCA-C is Benign according to our data. Variant chr14-28767485-CGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1123192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.218_220del	p.Gln73del	inframe_deletion	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.218_220del	p.Gln73del	inframe_deletion	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.218_220del	p.Gln73del	inframe_deletion	2/2			P1
LINC01551	ENST00000675861.1	n.374+1484_374+1486del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000278 AC: 4 AN: 143906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000202

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000460

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000538 AC: 49 AN: 910960 Hom.: 0 AF XY: 0.0000477 AC XY: 21 AN XY: 440222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000598

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000300

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.0000544

Gnomad4 OTH exome AF: 0.0000621

GnomAD4 genome AF: 0.0000278 AC: 4 AN: 143994 Hom.: 0 Cov.: 31 AF XY: 0.0000143 AC XY: 1 AN XY: 70064

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000460

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rett syndrome, congenital variant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 28, 2023

- -

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: rs398124201; hg19: chr14-29236691;