Genetic Variant FRA10AC1:c.-151_-149dupCGG (chr10-93702522-A-ACCG) – 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.-151_-149dupCGG 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 0.013 ( 48 hom., cov: 0)

Exomes 𝑓: 0.0060 ( 19 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

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0657 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.-151_-149dupCGG	5_prime_UTR	Exon 1 of 14	NP_660289.2
FRA10AC1	NM_001347712.2		c.-352_-350dupCGG	5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
FRA10AC1	NM_001347713.2		c.-271_-269dupCGG	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.-151_-149dupCGG	5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
FRA10AC1	ENST00000959343.1		c.-151_-149dupCGG	5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
FRA10AC1	ENST00000905754.1		c.-352_-350dupCGG	5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1852

AN:

147308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00483

Gnomad ASJ

AF:

0.00294

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.00741

Gnomad FIN

AF:

0.000505

Gnomad MID

AF:

0.00662

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00748

GnomAD4 exome

AF:

0.00598

AC:

410

AN:

68588

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

282

AN XY:

42832

show subpopulations

African (AFR)

AF:

0.0285

AC:

AN:

1016

American (AMR)

AF:

0.00823

AC:

AN:

2066

Ashkenazi Jewish (ASJ)

AF:

0.00102

AC:

AN:

976

East Asian (EAS)

AF:

0.0762

AC:

AN:

1194

South Asian (SAS)

AF:

0.00992

AC:

123

AN:

12402

European-Finnish (FIN)

AF:

0.00144

AC:

AN:

2786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.00229

AC:

102

AN:

44554

Other (OTH)

AF:

0.0128

AC:

AN:

3366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.587

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:

0.0126

AC:

1853

AN:

147424

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

917

AN XY:

71838

show subpopulations

African (AFR)

AF:

0.0316

AC:

1264

AN:

39992

American (AMR)

AF:

0.00483

AC:

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.00294

AC:

AN:

3396

East Asian (EAS)

AF:

0.0719

AC:

360

AN:

5010

South Asian (SAS)

AF:

0.00742

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

9900

Middle Eastern (MID)

AF:

0.00704

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

66416

Other (OTH)

AF:

0.00740

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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