rs112803404

Variant names:

• chr14-28767726-C-G
• rs112803404
• NM_005249.5:c.447C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-28767726-C-G
• chr14-28767726-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005249.5(FOXG1):​c.447C>G​(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000792 in 1,514,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A149A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: FOXG1 NM_005249.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.189
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 14-28767726-C-G is Benign according to our data. Variant chr14-28767726-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1214020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.189 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 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.447C>G	p.Ala149Ala	synonymous	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.447C>G	p.Ala149Ala	synonymous	Exon 1 of 1	ENSP00000339004.3
	FOXG1	ENST00000706482.1		c.447C>G	p.Ala149Ala	synonymous	Exon 2 of 2	ENSP00000516406.1
	LINC01551	ENST00000675861.1		n.374+1713C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149696 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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

GnomAD2 exomes AF: 0.0000153 AC: 2 AN: 131114 AF XY: 0.0000279

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000201

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000733 AC: 10 AN: 1364848 Hom.: 0 Cov.: 34 AF XY: 0.0000104 AC XY: 7 AN XY: 672992

African (AFR) AF: 0.00 AC: 0 AN: 31368

American (AMR) AF: 0.0000562 AC: 2 AN: 35612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24818

East Asian (EAS) AF: 0.00 AC: 0 AN: 35664

South Asian (SAS) AF: 0.00 AC: 0 AN: 78590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.00000752 AC: 8 AN: 1064270

Other (OTH) AF: 0.00 AC: 0 AN: 57058

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149696 Hom.: 0 Cov.: 32 AF XY: 0.0000274 AC XY: 2 AN XY: 73020

African (AFR) AF: 0.00 AC: 0 AN: 40876

American (AMR) AF: 0.000133 AC: 2 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00 AC: 0 AN: 4644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67214

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Rett syndrome, congenital variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		-0.19
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: rs112803404; hg19: chr14-29236932;