14-28766942-C-CA

Variant summary

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

The NM_005249.5(FOXG1):c.-338_-337insA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (33228 hom., cov: 0)
  • Exomes 𝑓: 0.53 (120 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.926

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 -10 ACMG points.

• BP6: Variant 14-28766942-C-CA is Benign according to our data. Variant chr14-28766942-C-CA is described in ClinVar as [Benign]. Clinvar id is 1229264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.-338_-337insA		5_prime_UTR_variant	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.-338_-337insA		5_prime_UTR_variant	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.-338_-337insA		5_prime_UTR_variant	2/2			P1
LINC01551	ENST00000675861.1	n.374+929_374+930insA		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.682 AC: 97274 AN: 142612 Hom.: 33188 Cov.: 0

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.665

GnomAD4 exome AF: 0.532 AC: 435 AN: 818 Hom.: 120 Cov.: 0 AF XY: 0.539 AC XY: 333 AN XY: 618

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.682 AC: 97360 AN: 142706 Hom.: 33228 Cov.: 0 AF XY: 0.682 AC XY: 47350 AN XY: 69424

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.669

Alfa AF: 0.396 Hom.: 706

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 19, 2019

- -

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: rs59954935; hg19: chr14-29236148;