rs148157138

Variant names:

• chr14-28767782-G-C
• rs148157138
• NM_005249.5:c.503G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-28767782-G-C
• chr14-28767782-G-T
• chr14-28767782-G-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BA1 BP4

This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Gly168Ala variant in FOXG1 is 0.18% in African sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). Computational analysis prediction tools suggest that the p.Gly168Ala variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Gly168Ala variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA314588/MONDO:0100040/016

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: FOXG1 NM_005249.5 missense
• Clinical Significance: Benign reviewed by expert panel B:7
• Conservation: PhyloP100: 3.88
• 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 -9 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

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.503G>C	p.Gly168Ala	missense	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.503G>C	p.Gly168Ala	missense	Exon 1 of 1	ENSP00000339004.3	P55316
	FOXG1	ENST00000706482.1		c.503G>C	p.Gly168Ala	missense	Exon 2 of 2	ENSP00000516406.1	P55316
	LINC01551	ENST00000675861.1		n.374+1769G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 151954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000128 AC: 30 AN: 234708 AF XY: 0.0000933

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.0000884

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000427 AC: 62 AN: 1451572 Hom.: 0 Cov.: 35 AF XY: 0.0000332 AC XY: 24 AN XY: 721954

African (AFR) AF: 0.00165 AC: 55 AN: 33424

American (AMR) AF: 0.0000900 AC: 4 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110510

Other (OTH) AF: 0.0000498 AC: 3 AN: 60186

GnomAD4 genome AF: 0.000434 AC: 66 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74340

African (AFR) AF: 0.00154 AC: 64 AN: 41534

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000525

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000149 AC: 18

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FOXG1 disorder (1)
-	-	1	FOXG1-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	Rett syndrome, congenital variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.21
Sift	Benign	0.051	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
Vest4		0.10
MVP		0.32
ClinPred		0.021	T
GERP RS		0.91
Varity_R		0.096
gMVP		0.64
Mutation Taster		=94/6	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: rs148157138; hg19: chr14-29236988;