Genetic Variant FRA10AC1:c.-157_-149dupCGGCGGCGG (chr10-93702522-A-ACCGCCGCCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_145246.5(FRA10AC1):c.-157_-149dupCGGCGGCGG 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 0.00056 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0014 ( 9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000556 (82/147430) while in subpopulation SAS AF = 0.00371 (17/4582). AF 95% confidence interval is 0.00236. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

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.-157_-149dupCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_660289.2
FRA10AC1	NM_001347712.2		c.-358_-350dupCGGCGGCGG	5_prime_UTR	Exon 1 of 14	NP_001334641.1	Q70Z53-1
FRA10AC1	NM_001347713.2		c.-277_-269dupCGGCGGCGG	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.-157_-149dupCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000360488.3	Q70Z53-1
FRA10AC1	ENST00000959343.1		c.-157_-149dupCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000629402.1
FRA10AC1	ENST00000905754.1		c.-358_-350dupCGGCGGCGG	5_prime_UTR	Exon 1 of 14	ENSP00000575813.1

Frequencies

GnomAD3 genomes

AF:

0.000550

AC:

AN:

147314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000597

Gnomad SAS

AF:

0.00392

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00141

AC:

AN:

68608

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

AN XY:

42846

show subpopulations

African (AFR)

AF:

0.000982

AC:

AN:

1018

American (AMR)

AF:

0.00

AC:

AN:

2066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

976

East Asian (EAS)

AF:

0.00

AC:

AN:

1204

South Asian (SAS)

AF:

0.00637

AC:

AN:

12402

European-Finnish (FIN)

AF:

0.000359

AC:

AN:

2786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.000292

AC:

AN:

44560

Other (OTH)

AF:

0.000891

AC:

AN:

3368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.598

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000556

AC:

AN:

147430

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

AN XY:

71838

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

40002

American (AMR)

AF:

0.0000671

AC:

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.000599

AC:

AN:

5010

South Asian (SAS)

AF:

0.00371

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000136

AC:

AN:

66414

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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

Splicing

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

Publications

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10-93702522-ACCGCCGCCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over