14-28767055-C-CT

Position:

• chr14-28767055-C-CT

Variant summary

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

The NM_005249.5(FOXG1):​c.-210dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 143,102 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (9 hom., cov: 29)
  • Exomes 𝑓: 0.053 (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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-28767055-C-CT is Benign according to our data. Variant chr14-28767055-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1211390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5	c.-210dupT		5_prime_UTR_variant	1/1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXG1	ENST00000313071	c.-210dupT		5_prime_UTR_variant	1/1		NM_005249.5	ENSP00000339004.3
FOXG1	ENST00000706482	c.-210dupT		5_prime_UTR_variant	2/2			ENSP00000516406.1
LINC01551	ENST00000675861.1	n.374+1057dupT		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00942 AC: 1316 AN: 139664 Hom.: 9 Cov.: 29

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00882

Gnomad ASJ AF: 0.00790

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.000389

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00623

Gnomad OTH AF: 0.00843

GnomAD4 exome AF: 0.0529 AC: 182 AN: 3438 Hom.: 0 Cov.: 0 AF XY: 0.0534 AC XY: 105 AN XY: 1968

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.0917

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0490

Gnomad4 OTH exome AF: 0.0566

GnomAD4 genome AF: 0.00941 AC: 1314 AN: 139664 Hom.: 9 Cov.: 29 AF XY: 0.00922 AC XY: 623 AN XY: 67596

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00881

Gnomad4 ASJ AF: 0.00790

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.00501

Gnomad4 FIN AF: 0.000389

Gnomad4 NFE AF: 0.00623

Gnomad4 OTH AF: 0.00839

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 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;