NM_005249.5:c.-210delT

Variant names:

• chr14-28767055-CT-C
• rs542787885
• NM_005249.5:c.-210delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005249.5(FOXG1):​c.-210delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 143,078 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (18 hom., cov: 29)
  • Exomes 𝑓: 0.068 (0 hom.)
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490
• Publications: 0 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-28767055-CT-C is Benign according to our data. Variant chr14-28767055-CT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1188300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1522/139646) while in subpopulation AFR AF = 0.0337 (1291/38302). AF 95% confidence interval is 0.0322. There are 18 homozygotes in GnomAd4. There are 726 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1522 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.-210delT		5_prime_UTR	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.-210delT		5_prime_UTR	Exon 1 of 1	ENSP00000339004.3	P55316
	FOXG1	ENST00000706482.1		c.-210delT		5_prime_UTR	Exon 2 of 2	ENSP00000516406.1	P55316
	LINC01551	ENST00000675861.1		n.374+1057delT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1524 AN: 139646 Hom.: 18 Cov.: 29

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00626

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.00165

Gnomad SAS AF: 0.000905

Gnomad FIN AF: 0.000130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0685 AC: 235 AN: 3432 Hom.: 0 Cov.: 0 AF XY: 0.0759 AC XY: 149 AN XY: 1962

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

African (AFR) AF: 0.0400 AC: 2 AN: 50

American (AMR) AF: 0.200 AC: 6 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22

East Asian (EAS) AF: 0.0357 AC: 1 AN: 28

South Asian (SAS) AF: 0.119 AC: 55 AN: 464

European-Finnish (FIN) AF: 0.0459 AC: 9 AN: 196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.0626 AC: 158 AN: 2522

Other (OTH) AF: 0.0385 AC: 4 AN: 104

⚠️ 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: 0.0109 AC: 1522 AN: 139646 Hom.: 18 Cov.: 29 AF XY: 0.0107 AC XY: 726 AN XY: 67582

African (AFR) AF: 0.0337 AC: 1291 AN: 38302

American (AMR) AF: 0.00625 AC: 88 AN: 14080

Ashkenazi Jewish (ASJ) AF: 0.000304 AC: 1 AN: 3290

East Asian (EAS) AF: 0.00165 AC: 8 AN: 4836

South Asian (SAS) AF: 0.000911 AC: 4 AN: 4390

European-Finnish (FIN) AF: 0.000130 AC: 1 AN: 7720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00170 AC: 109 AN: 63980

Other (OTH) AF: 0.0105 AC: 20 AN: 1908

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs542787885; hg19: chr14-29236261;