rs587783630

Variant names:

• chr14-28767417-GCACCACCACCACCAC-G
• rs587783630
• NM_005249.5:c.147_161delCCACCACCACCACCA

Your query was ambiguous. Multiple possible variants found:

• chr14-28767417-GCACCACCACCACCAC-G
• chr14-28767417-GCACCACCACCACCAC-GCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCACCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCACCACCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCACCACCACCACCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCACCACCACCACCACCAC
• chr14-28767417-GCACCACCACCACCAC-GCACCACCACCACCACCACCACCAC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005249.5(FOXG1):​c.147_161delCCACCACCACCACCA​(p.His50_His54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,385,644 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 30)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: FOXG1 NM_005249.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• 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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005249.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.147_161delCCACCACCACCACCA	p.His50_His54del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071.7	c.147_161delCCACCACCACCACCA	p.His50_His54del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482.1	c.147_161delCCACCACCACCACCA	p.His50_His54del	disruptive_inframe_deletion	Exon 2 of 2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+1413_374+1427delCCACCACCACCACCA		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00000699 AC: 1 AN: 143126 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.000517

GnomAD4 exome AF: 8.05e-7 AC: 1 AN: 1242518 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 615222

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25398

American (AMR) AF: 0.00 AC: 0 AN: 30694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19030

East Asian (EAS) AF: 0.00 AC: 0 AN: 24694

South Asian (SAS) AF: 0.00 AC: 0 AN: 72994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4008

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 978040

Other (OTH) AF: 0.0000213 AC: 1 AN: 46878

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000699 AC: 1 AN: 143126 Hom.: 0 Cov.: 30 AF XY: 0.0000144 AC XY: 1 AN XY: 69430

African (AFR) AF: 0.00 AC: 0 AN: 39358

American (AMR) AF: 0.00 AC: 0 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.00 AC: 0 AN: 4890

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65052

Other (OTH) AF: 0.000517 AC: 1 AN: 1936

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=158/42	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs587783630; hg19: chr14-29236623;