Genetic Variant FRA10AC1:c.-154_-149dupCGGCGG (chr10-93702522-A-ACCGCCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_145246.5(FRA10AC1):c.-154_-149dupCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0022 ( 40 hom. )

Consequence

FRA10AC1
NM_145246.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

1 publications found

Variant links:

Genes affected

FRA10AC1 (HGNC:1162): (FRA10A associated CGG repeat 1) The protein encoded by this gene is a nuclear phosphoprotein of unknown function. This gene contains a tandem CGG repeat region within a CpG island that normally consists of 8-14 repeats but can expand to over 200 repeats. The repeat region is within the 5' UTR of some transcript variants, but is intronic to another variant. The expanded repeat allele is a fragile site and becomes hypermethylated, causing a reduction in gene expression. A disease phenotype has not been associated with expanded alleles. This gene is found within the rare FRA10A folate-sensitive fragile site. [provided by RefSeq, Dec 2016]

FRA10AC1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P

FRA10AC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145246.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRA10AC1	NM_145246.5	MANE Select	c.-154_-149dupCGGCGG	5_prime_UTR	Exon 1 of 14	NP_660289.2
FRA10AC1	NM_001347712.2		c.-355_-350dupCGGCGG	5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
FRA10AC1	NM_001347713.2		c.-274_-269dupCGGCGG	5_prime_UTR	Exon 1 of 15	NP_001334642.1	Q70Z53-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRA10AC1	ENST00000359204.5	TSL:1 MANE Select	c.-154_-149dupCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
FRA10AC1	ENST00000959343.1		c.-154_-149dupCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
FRA10AC1	ENST00000905754.1		c.-355_-350dupCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

257

AN:

147318

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00161

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.00240

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00199

GnomAD4 exome

AF:

0.00222

AC:

152

AN:

68608

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

AN XY:

42850

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

1018

American (AMR)

AF:

0.00484

AC:

AN:

2066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.0880

AC:

106

AN:

1204

South Asian (SAS)

AF:

0.000726

AC:

AN:

12400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2786

Middle Eastern (MID)

AF:

0.00439

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.000224

AC:

AN:

44564

Other (OTH)

AF:

0.00416

AC:

AN:

3366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.645

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00175

AC:

258

AN:

147434

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

135

AN XY:

71842

show subpopulations

African (AFR)

AF:

0.00355

AC:

142

AN:

40004

American (AMR)

AF:

0.00161

AC:

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.0140

AC:

AN:

5010

South Asian (SAS)

AF:

0.00240

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000105

AC:

AN:

66414

Other (OTH)

AF:

0.00197

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over