rs1555321214

Variant names:

• chr14-28767459-G-C
• rs1555321214
• NM_005249.5:c.180G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005249.5(FOXG1):​c.180G>C​(p.Pro60Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXG1 NM_005249.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.977
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 14-28767459-G-C is Benign according to our data. Variant chr14-28767459-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 471464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.977 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.180G>C	p.Pro60Pro	synonymous	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.180G>C	p.Pro60Pro	synonymous	Exon 1 of 1	ENSP00000339004.3
	FOXG1	ENST00000706482.1		c.180G>C	p.Pro60Pro	synonymous	Exon 2 of 2	ENSP00000516406.1
	LINC01551	ENST00000675861.1		n.374+1446G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1039840 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 505416

African (AFR) AF: 0.00 AC: 0 AN: 21070

American (AMR) AF: 0.00 AC: 0 AN: 19898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14540

East Asian (EAS) AF: 0.00 AC: 0 AN: 16406

South Asian (SAS) AF: 0.00 AC: 0 AN: 41722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 864526

Other (OTH) AF: 0.00 AC: 0 AN: 37764

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rett syndrome, congenital variant Benign:1

Jun 04, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.98
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: rs1555321214; hg19: chr14-29236665;