rs587783632

chr14-28767450-CCCGCCGCCGCCCGCCCCGCAACCG-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_005249.5(FOXG1):c.183_206del(p.Ala62_Pro69del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,198,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: FOXG1 NM_005249.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.94

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 -12 ACMG points.

• BP6: Variant 14-28767450-CCCGCCGCCGCCCGCCCCGCAACCG-C is Benign according to our data. Variant chr14-28767450-CCCGCCGCCGCCCGCCCCGCAACCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 158590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.183_206del	p.Ala62_Pro69del	inframe_deletion	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.183_206del	p.Ala62_Pro69del	inframe_deletion	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.183_206del	p.Ala62_Pro69del	inframe_deletion	2/2			P1
LINC01551	ENST00000675861.1	n.374+1449_374+1472del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000485 AC: 7 AN: 144262 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000206

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000307

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000135 AC: 11 AN: 81572 Hom.: 0 AF XY: 0.000172 AC XY: 8 AN XY: 46508

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000485

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 31 AN: 1053810 Hom.: 0 AF XY: 0.0000389 AC XY: 20 AN XY: 513900

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000116

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000918

Gnomad4 OTH exome AF: 0.0000523

GnomAD4 genome AF: 0.0000485 AC: 7 AN: 144346 Hom.: 0 Cov.: 31 AF XY: 0.0000854 AC XY: 6 AN XY: 70236

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000206

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000307

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2012	The variant is found in EPILEPSY panel(s). -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Rett syndrome, congenital variant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587783632; hg19: chr14-29236656;