10-93702522-ACCG-A

Position:

• chr10-93702522-ACCG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145246.5(FRA10AC1):​c.-151_-149delCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 213,674 control chromosomes in the GnomAD database, including 20,973 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (14512 hom., cov: 0)
  • Exomes 𝑓: 0.41 (6461 hom.)
• Consequence: FRA10AC1 NM_145246.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRA10AC1	NM_145246.5	c.-151_-149delCGG		5_prime_UTR_variant	1/14	ENST00000359204.5	NP_660289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRA10AC1	ENST00000359204.5	c.-151_-149delCGG		5_prime_UTR_variant	1/14	1	NM_145246.5	ENSP00000360488.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 60405 AN: 147156 Hom.: 14517 Cov.: 0

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.410 AC: 27207 AN: 66402 Hom.: 6461 AF XY: 0.415 AC XY: 17141 AN XY: 41326

Gnomad4 AFR exome AF: 0.0709

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.410 AC: 60403 AN: 147272 Hom.: 14512 Cov.: 0 AF XY: 0.414 AC XY: 29726 AN XY: 71754

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs139811637; hg19: chr10-95462279;