chr14-28767497-AGCCGCCGCC-A

Variant names:

• chr14-28767497-AGCCGCCGCC-A
• rs786200975
• NM_005249.5:c.228_236delGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_005249.5(FOXG1):​c.228_236delGCCGCCGCC​(p.Pro77_Pro79del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000613 in 978,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: FOXG1 NM_005249.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005249.5
• BP6: Variant 14-28767497-AGCCGCCGCC-A is Benign according to our data. Variant chr14-28767497-AGCCGCCGCC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1094650.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000339004.3
	FOXG1	ENST00000706482.1		c.228_236delGCCGCCGCC	p.Pro77_Pro79del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000516406.1
	LINC01551	ENST00000675861.1		n.374+1494_374+1502delGCCGCCGCC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000214 AC: 3 AN: 139878 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000777

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 3 AN: 838494 Hom.: 0 AF XY: 0.00000251 AC XY: 1 AN XY: 398112

African (AFR) AF: 0.000192 AC: 3 AN: 15642

American (AMR) AF: 0.00 AC: 0 AN: 2948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6304

East Asian (EAS) AF: 0.00 AC: 0 AN: 8344

South Asian (SAS) AF: 0.00 AC: 0 AN: 18110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 748524

Other (OTH) AF: 0.00 AC: 0 AN: 28798

GnomAD4 genome AF: 0.0000214 AC: 3 AN: 139878 Hom.: 0 Cov.: 31 AF XY: 0.0000294 AC XY: 2 AN XY: 68002

African (AFR) AF: 0.0000777 AC: 3 AN: 38588

American (AMR) AF: 0.00 AC: 0 AN: 14230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3276

East Asian (EAS) AF: 0.00 AC: 0 AN: 4700

South Asian (SAS) AF: 0.00 AC: 0 AN: 4428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63692

Other (OTH) AF: 0.00 AC: 0 AN: 1898

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rett syndrome, congenital variant Benign:1

Jul 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=180/20	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs786200975; hg19: chr14-29236703;